Mutagenesis, Vol. 17, No. 2, 149-156,
March 2002
© 2002 UK Environmental Mutagen Society/Oxford University Press
REVIEW |
p53 regulation of DNA excision repair pathways
Indiana University Cancer Center, Department of Microbiology, Walther Oncology Center, Indiana University School of Medicine, and Walther Cancer Institute, Indianapolis, IN 46202, USA
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Abstract |
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 Top Abstract Historical significanceRole for p53 in...Role for p53 in...Relationship of p53, NER...Implications for...The DNA repair branch...References |
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The regulation of DNA excision repair pathways by p53 and its downstream genes is an emerging body of literature, largely distinct and separable from the more-studied cell cycle arrest and apoptosis responses regulated by p53. Regulation of nucleotide excision repair of UV-damage by p53 and its downstream genes Gadd45 and p48XPE has been well-documented, but much remains to be done in elucidating mechanisms. Moreover, p53 also participates in base excision repair of hydrogen peroxide-induced damage, still at an early stage of investigation. In human cancers carrying inactivating mutations in p53, especially those wherein p53 mutation occurs early, accelerated mutagenesis by exogenous and endogenous DNA damage is predicted. At the same time, the excision repair pathways could provide a useful target for DNA-damaging chemotherapeutics against p53-defective cancers, having decreased ability to repair chemotherapeutic damage. To our knowledge, this is the first review to address this emerging field.
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Historical significance |
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TopAbstractHistorical significanceRole for p53 in...Role for p53 in...Relationship of p53, NER...Implications for...The DNA repair branch...References |
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It has long been envisaged that p53 protects the genome from potentially mutagenic DNA damage. The first evidence of protection stemmed from the finding that p53 mediated a G1 cell cycle checkpoint in response to ionizing radiation (IR) damage (Kastan et al., 1992
). A high fraction of human cancers that had mutated p53 had lost the G1 checkpoint and failed to arrest the cell cycle after IR (Kastan et al., 1992). The conventional wisdom was that by arresting cells in G1 (later shown to be due to the p53 transcriptionally induced protein p21Waf1/Cip1/Sdi1; Harper et al., 1993), p53 promoted DNA repair in a sense by providing more time for repair to take place prior to S phase entry. This view is probably largely true (Sheikh et al., 1997), but is a simplified view given our current knowledge of the effectors of the p53 pathway and cellular responses to different classes of DNA-damaging agents (Meyer et al., 1999). In this review we consider the various classes of DNA damage and the role of p53 and its downstream genes in cellular responses to the agents and revisit early studies where applicable. |
Role for p53 in nucleotide excision repair (NER) |
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TopAbstractHistorical significanceRole for p53 in...Role for p53 in...Relationship of p53, NER...Implications for...The DNA repair branch...References |
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As discussed, early paradigms of p53 function were based on the use of IR to induce DNA damage. However, in order to be versatile as a tumor suppressor and protect the cell from heterogeneous DNA damage from endogenous and exogenous sources, it seemed logical that p53 would also be activated by other classes of DNA damage. Indeed, treatment of cells with UV radiation and other DNA-damaging agents was effective in activating p53 as a transcription factor and in turn up-regulating its downstream effector genes, including p21Waf1/Cip1/Sdi1 (Zhan et al., 1993
). By all available criteria, including the induction of a p53-responsive promoter/reporter plasmid (13 p53-binding sites fused to a basal promoter to drive a reporter gene), UV radiation was at least as effective an inducer of p53 as was IR (Zhan et al., 1993). In the Zhan study and many others, p53 activity was defined by its ability to transactivate gene promoters with a consensus p53-binding site (El-Deiry et al., 1992), as well as synthetic promoter constructs such as pG13-CAT decribed above. The biological functions associated with p53 are mostly due to the activities of p53-regulated gene products, for example as determined through the use of gene knockouts of the downstream effectors (Smith et al., 2000). As discussed, whether p53 protein could exert some direct effects has long been debated and is hard to exclude.
In order to specifically address a role for p53 in the observed DNA damage responses, matched pairs of p53 wild-type and p53 mutant cell lines were used (Kastan et al., 1992). As was the case with IR, sublethal doses of UV radiation arrested p53 wild-type cells in G1, while p53 mutant cells failed to arrest (Zhan et al., 1996). Higher doses of UV radiation, however, produced a more complex cell cycle arrest response (Zhan et al., 1996; Li and Ho, 1998; Chang et al., 1999). Beyond cell cycle responses, DNA repair of, and sensitivity to, UV-induced DNA damage were specifically assayed (Smith et al., 1995). Cells lacking functional p53 exhibited defective repair of UV damage (Smith et al., 1995; Ford and Hanawalt, 1995) and were more sensitive to UV irradiation than their wild-type p53 counterparts (Smith et al., 1995; Havre et al., 1995; Ford et al., 1998; Cistulli and Kaufman, 1998; El-Mahdy et al., 2000; McKay et al., 2000). Hence, the conclusion by several groups was that p53 played a role in DNA repair of UV damage by the nucleotide excision repair (NER) pathway (Levine, 1997).
A role for p53 in NER was supported by experimental data obtained from various types of assays. One approach, using T4 endonuclease mapping of genomic DNA in UV-irradiated cells, showed that p53 affected the removal of UV-induced cyclobutane pyrimidine dimers (CPDs) from the non-transcribed strand of the endogenous dihydrofolate reductase (DHFR) gene, while the transcribed strand was unaffected (Wang,X.W. et al., 1995; Ford and Hanawalt, 1995, 1997). The significance of this finding was that p53 affected the global genomic repair (GGR) subpathway of NER, while the transcription-coupled repair (TCR) subpathway of NER was unaffected (however, see Zhu et al., 2000; and discussion below). Another approach utilized host cell reactivation (HCR) of a UV-irradiated reporter plasmid in isogenic matched cells carrying wild-type or mutant p53 (Smith et al., 1995). The assay relies on the ability of the cell to repair the transiently transfected plasmids and thereby restore reporter gene expression (Ganesan et al., 1999). Cells with wild-type p53 showed 3-fold higher levels of reactivation than did p53 mutant cells (Smith et al., 1995). Yet a third approach utilized a UV-damaged `shuttle' vector, which was introduced into p53 wild-type or p53-defective cells and then retrieved by transformation of competent Escherichia coli. Colonies carrying mutations within the shuttle plasmid are identified by a blue/white screen, so that mutation frequencies for each cell line may be calculated. Normal p53 resulted in a decreased mutation frequency, commensurate with increased DNA repair, and also showed that the correct sequence information was restored in the presence of functional p53 (Yuan et al., 1995). Thus, a number of independent criteria established that p53 enhanced the level and fidelity of NER.
One viewpoint of the HCR assays is that they measure TCR (of the expressed reporter gene), consistent with evidence that p53 may contribute in a small way to TCR and not just GGR (Zhu et al., 2000). However, a comprehensive study of HCR was conducted by Ganesan et al. (1999), who showed, using TCR- or GGR-defective cell lines, that both GGR and TCR contribute to host cell reactivation (Ganesan et al., 1999). The authors reported that the strength of the promoter element was one factor that affected TCR and, at least in some cell types, GGR may be occurring at a sufficient rate to effectively mask TCR. Hence, the HCR and shuttle vector experiments measure DNA repair attributed to both the GGR and TCR pathways, consistent with data that p53 largely affects GGR (Ford and Hanawalt, 1997), but may also affect TCR, albeit to a lesser degree (Zhu et al., 1999).
One unanswered question was whether p53 protein was a direct participant in DNA repair, specifically NER repair, or whether the aforementioned observations were due to p53-regulated gene products. Because cell-based systems could not make this distinction, i.e. cells lacking functional p53 often exhibit decreased levels of downstream effector proteins (Smith et al., 1995), assays of NER in vitro were employed. Given evidence that p53 protein interacts with TFIIH (Wang,X.W. et al., 1995), a component of the NER repairosome complex, one could envision that the addition of recombinant p53 to assays of NER in vitro might enhance the reactions. However, p53 protein added in vitro did not produce an enhancement of NER (Leveillard et al., 1996). One interpretation was that p53-regulated gene products, and not p53 itself, mediated the NER response and, therefore, the response would not be observed by addition of recombinant p53, as found by Leveillard. The downstream effectors of p53 are further discussed below. We considered another possibility, that presumably p53 must bind to TFIIH or another component of the NER complex in order to affect the NER reaction and that recombinant p53 protein could conceivably lack a post-translational modification, assembly into higher order structures or other native property necessary for its putative role in NER. We took a different approach (Smith et al., 1995), employing extracts from p53 wild-type cells, which were then immunodepleted of almost all p53 protein (Figure 1). By this approach, not only should p53 be depleted, but any p53-bound proteins such as TFIIH may also be depleted. However, the immunodepletion of p53 had no measurable effect on NER in vitro (Figure 1). We and others concluded that the p53-mediated NER response is probably mediated through p53-regulated gene products. On the other hand, the contrasting viewpoints, direct p53 action versus p53 action through its downstream gene products, may not be mutually exclusive. Recently, p33, a member of the p53 gene family, was shown to interact physically with (p53-regulated protein) Gadd45 and affect repair of UV damage in a p53-dependent manner (Cheung et al., 2001).
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-32P]dCTP (10 µCi/lane). Hence, the incorporation of radiolabeled nucleotide is a measure of NER (Smith et al., 1995At least three p53-regulated genes have been found to contribute to NER. Two gene products associated with the cancer-prone genetic disease xeroderma pigmentosum, p48XPE and XPC, are specifically p53-regulated (Hwang et al., 1999
; Amundson et al., 2000). Both are DNA damage-binding protreins (DDBs) involved in the recognition of DNA damage and both are implicated in the GGR subpathway of NER. A third p53-regulated protein is Gadd45, which binds to UV-damaged DNA in vitro (Carrier et al., 1999) and may, therefore, also play a role in damage recognition. Gadd45-null mice have been generated and they exhibit an NER defect (Smith et al., 2000; Hollander et al., 2001). Much remains to be done, however, in determining the mechanisms of action of these proteins. Of what is known about p48XPE, it binds with high affinity to CPDs in UV-damaged DNA and is thought to be an early effector of a damage recognition cascade. After p48XPE binds to the damaged site, lower affinity NER repair proteins are recruited to the site and affect repair. Interestingly, Gadd45 was also shown to bind to UV-damaged DNA and chromatin in vitro (Carrier et al., 1999). The implication is that p48XPE and Gadd45 may be directly involved in damage recognition, suggesting a role in the early steps of the NER process.
As discussed, it is conceivable that p53 protein may itself be involved in NER, evident by its binding to DNA damage (Yamane et al., 2001). The same could be said of other homologs of p53, e.g. p73 and p63 (Dohn et al., 2001), although potential roles for these proteins in NER have been the subject of almost no studies. One study did show that p73 induced an NER response and protected cells from DNA damage (Vikhanskaya et al., 2001). The study did not address whether p73 acted directly in NER or whether the effect was due to effector genes induced by p73, some of which, like Gadd45, are also regulated by p53. Although outside the scope of this review, Gadd45 is also regulated by BRCA1 (Jin et al., 2000), the implication being that tumor suppressor proteins may converge on an inducible DNA repair end point in at least some cellular contexts.
It should be noted that p53-regulated proteins are often present at appreciable basal levels and that in fact p53 is responsible for maintaining basal transcription of its downstream genes in some cell types, particularly epithelial cell lines and fibroblasts (Smith et al., 1995; Cistulli and Kaufmann, 1998; Ford et al., 1998). The implication for NER is that repair can initiate immediately after DNA damage. This is an important point, as the bulk of NER normally occurs within 3 h after DNA damage, probably not allowing for full induction of p53-regulated effectors. Basal transcription of p53-regulated genes, in a p53-dependent manner (Cistulli and Kaufmann, 1998), facilitates temporal coupling between the p53 pathway and cellular NER (Ford and Hanawalt, 1997).
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Role for p53 in base excision repair (BER) |
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TopAbstractHistorical significanceRole for p53 in...Role for p53 in...Relationship of p53, NER...Implications for...The DNA repair branch...References |
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As mentioned, a number of different classes of DNA-damaging agents can elicit p53 activation as a transcription factor in inducing its downstream genes. At the same time, the lesion frequencies and types of damages differ markedly, certainly in comparing agents as diverse as IR and UV (Meyer et al., 1999
). Yet a third prototypical class of DNA damage is base damage, commonly associated with oxidative stress processes. One compound that induces only base damage is methylmethane sulfonate (MMS), which generates primarily alkylation of the N7 position of guanine residues. The lesions are then processed through an abasic site intermediate, a process known as base excision repair (BER). In contrast to NER, the BER repairosome complex is composed of only four to six proteins (the more intricate NER repairosome is composed of 20 or more). Relevant to this review, BER has been found to be regulated by p53 and is deficient in p53-null cells (Offer et al., 2001; Zhou et al., 2001). Given the apparent dissimilarities between NER and BER, this might seem surprising (Stucki et al., 1998). On the other hand, p53 regulates perhaps as many as 100 proteins (Tokino et al., 1994) and, therefore, it is not beyond reason that genes involved in BER might be candidates for regulation by p53. One gene product required for BER that is affected by the presence or absence of p53 is DNA polymerase ß (ß-pol), the enzyme involved in BER repair synthesis. Specifically, ß-pol repair synthesis in vitro was affected by p53, even when p53 was added as a recombinant protein (Zhou et al., 2001). Therefore, in contrast to NER, the evidence for a direct role for p53 protein in BER is much stronger. Studies of the regulation of BER by p53 are still at an early stage. If history is a guide, additional links between the p53 pathway and BER are likely to be revealed. For example, two subpathways of BER have been identified: `short patch' BER and `long patch' BER (Matsumoto et al., 1999). The former mechanism is responsible for single nucleotide replacements, while the latter favors nucleotide replacements of up to six bases. It is not known whether p53 affects both BER subpathways. Because long patch BER involves DNA polymerases 
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(Stucki et al., 1998), subunits that are also shared with NER, it is conceivable that p53 could simultaneously affect both BER and NER by a common, as yet unknown, mechanism (Tanaka et al., 2000). |
Relationship of p53, NER and BER to cell cycle regulation |
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TopAbstractHistorical significanceRole for p53 in...Role for p53 in...Relationship of p53, NER...Implications for...The DNA repair branch...References |
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The role of p53 in regulation of NER and BER repair responses involves a number of downstream effectors and is thus fairly complex. The early prediction was that p53, through its downstream effector p21Waf1/Cip1/Sdi1, a cyclin-dependent kinase inhibitor, would facilitate DNA repair by allowing cells to remain in G1 for a longer time before they resume cycling. This view is probably largely true, although surprisingly few studies have actually measured DNA repair in the context of cell cycle control. A prediction is that if G1 arrest is required for DNA repair, then cells lacking p21 genes would exhibit a repair deficit. Different groups have reported mixed findings regarding the DNA repair phenotype of p21-null cells (McDonald et al., 1996
; Fan et al., 1997; Smith et al., 2000; Adimoolam et al., 2001). Of course, the possibility remained that p21 could have functions unrelated to its role as a Cdk inhibitor, suggested for example by its interaction with PCNA (Stivala et al., 2001). Therefore, repair defects reported in p21-null cells could be independent of Cdk inhibition. We took a different approach to the problem, by asking whether p53-defective cells exhibit deficient DNA repair throughout the cell cycle. Although this remains a complex issue, one approach that we used was to measure unscheduled DNA synthesis (UDS), i.e. non-replicative synthesis, or repair synthesis, which occurs in G1 and G2 nuclei (Smith et al., 2000) (Figure 2). UDS was measured 3 h after UV irradiation. It has long been known that NER of UV damage is repaired at a constant rate throughout the cell cycle (reviewed in Smith and Fornace, 1997). On the other hand, the earlier studies were not designed to address any potential contribution by p53. That p53 regulation of NER is not dependent on cell cycle was shown by applying the UDS technique to serum-starved (non-cycling) cells, in which the capacity to G1 arrest is irrelevant (Smith et al., 2000). Another approach taken was to use cell lines lacking p21Waf1/Cip1/Sdi1 genes, which lack the ability to undergo G1 arrest. Reports of p21 involvement in NER have been contradictory (Fan et al., 1997; Sheikh et al., 1997; Adimoolam et al., 2001) even though, as discussed, it is possible that p21 may affect NER independent of its cyclin-dependent kinase function (Stivala et al., 2001). It is also conceivable that assays used by some of the laboratories may reveal a role for p21, while others do not, depending on the specific stage of the NER process that is affected by p21. One study suggests that it may act at a late stage of the process, such as in completion of the repair synthesis tracts (Stivala et al., 2001). Another approach was to use cells lacking Rb genes, which, like p21-deficient cells, lack the ability to arrest in G1. Using host cell reactivation, we observed no NER deficiency in Rb-deficient cells (Smith et al., 1995) nor were any differences observed in UDS (Smith et al., 2000) (Figure 3). We therefore conclude that neither p21 nor Rb deficiency can recapitulate the NER defect seen in p53-deficient cells (Adimoolam et al., 2001). On the other hand, cells lacking the Gadd45 (Smith et al., 2000), p48-XPE (Hwang et al., 1999) or XPC gene (Cheo et al., 1997) fully recapitulate the NER defect observed in p53-deficient cells, lending strong support to the idea that NER is mediated largely by these p53-regulated effectors.
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Val) transgenes exhibited an ~3-fold NER deficit, while cells with Rb blocked by HPV16-E7 (E7) showed normal levels of NER. (B) UDS of MEFs. UDS was performed 3 h after UV irradiation as in Figure 2
In the case of BER responses to base-damaging agents, fewer studies have been conducted. It is clear that ß-pol is the target of p53 activity in BER and one report indicates that p53 regulates BER in G1 (Offer et al., 2001
). If this holds true, then one might predict that p21 and/or Rb deficiencies affect BER indirectly by affecting G1 arrest. More studies are needed in order to draw any strong conclusions about the relationship of p53, BER and cell cycle control. A current overview of the relation of p53 to the NER and BER DNA repair pathways, respectively, is shown in Figures 4 and 5.
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Implications for chemotherapeutics |
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TopAbstractHistorical significanceRole for p53 in...Role for p53 in...Relationship of p53, NER...Implications for...The DNA repair branch...References |
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Over half of all human cancers carry mutant or inactive p53. Obviously, the NER and BER repair pathways are predicted to be deficient in p53 mutant cancers (Smith et al., 1995
; Seo et al., 2001b). Cancer chemotherapeutic drugs, such as oxaliplatin, cyclophosphamide and thio-TEPA (N,N',N''-triethylenethiophosphoramide), are DNA-damaging agents that produce both NER and BER type damages (Xu,Y. et al., 2001). One implication is that p53 mutant cancers may exhibit preferential sensitivity to at least some of these agents. Indeed, p53 mutant brain cancers were more sensitive to temozolomide (Hirose et al., 2001) and 1,3-bis(2-chloroethyl)-1-nitrosourea (Xu,G.W. et al., 2001). Mutant p53 breast cancer lines were more sensitive to oxaliplatin and thio-TEPA (Seo et al., 2001a), similar to results obtained with an experimental platinum compound in a mouse xenograft model (Pratesi et al., 1999). The reported sensitivities are generally modest (2- to 3-fold), but nonetheless could be therapeutically important (Hawkins et al., 1996; Brown and Wouters, 1999; Fan and Bertino, 1999). The reasons for modest sensitivity are probably several. (i) p53 primarily affects the GGR subpathway of NER (and presumably BER). In comparison with TCR, the contribution of GGR to cellular sensitivity is modest. On the other hand, p53 has been reported to modestly affect TCR (Zhu et al., 2000) and this minor contribution to TCR might be relevant to DNA damage sensitivity. (ii) In some cell types p53-mediated DNA repair may be counterbalanced by the opposing response of apoptosis, also regulated in part by p53 (Ford and Hanawalt, 1995; McKay et al., 2000). (iii) Agents other than UV radiation have been little studied. Note too that preferential sensitivity of p53 mutant cells can be enhanced by combination chemotherapeutics, e.g. the inclusion of 7-hydroxystaurosporine (UCN01) together with the aforementioned DNA-damaging agents (Wang,Q. et al., 1996). One report showed that UCN01 induced a higher fraction of cytotoxic strand breaks in p53 mutant cells (Jones et al., 2000). Thus, there appears to be much potential to exploit DNA repair defects in p53 mutant cancers. |
The DNA repair branch of the p53 pathway in carcinogenesis and cancer chemoprevention |
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TopAbstractHistorical significanceRole for p53 in...Role for p53 in...Relationship of p53, NER...Implications for...The DNA repair branch...References |
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As discussed, p53 primarily affects the GGR subpathway of NER. Importantly, cancer-prone genetic diseases, e.g. xeroderma pigmentosum groups C and E, likewise affect GGR but not TCR. Thus, GGR defects, even fairly modest ones, e.g. XPC and XPE, are potent predisposing factors in carcinogenesis (Friedberg et al., 1995
). It is therefore likely that the GGR defect associated with p53 contributes substantially to carcinogenesis in p53-defective conditions, e.g. Li–Fraumeni syndrome, a cancer-prone disease in which mutant p53 alleles are transmitted in the germline. Hence, wild-type p53 likely prevents carcinogenesis, at least in part, by maintaining GGR repair. Cells lacking fully functional p53, e.g. Li–Fraumeni syndrome, are GGR deficient (Ford and Hanawalt, 1995). Of the spectrum of Li–Fraumeni-associated tumors, breast cancer is one of the more frequent (Nichols et al., 2001). Internal tissues are not exposed to appreciable UV radiation, however, endogenous DNA damage associated with reactive oxygen species can produce over 10 000 potentially mutagenic (if not repaired) lesions per cell per day (Ames and Gold, 1997). The bulk of endogenous damage is base damage, repaired by BER, which we now know to be regulated by p53, while a small subset of lesions are repaired by NER (Kuraoka et al., 2000), also regulated by p53 (Zhou et al., 2001). The relative contributions of the different classes of lesions to human carcinogenesis are not known.
Thus, if agents are found that enhance the activity of wild-type p53, carcinogenesis may be inhibited or delayed. One such agent is the Bowman–Birk protease inhibitor, derived from soybeans, which up-regulates p53 and its downstream gene Gadd45 and increases cellular DNA repair (Dittmann et al., 1998a,b). It is likely that increased levels of DNA repair would result in a net decrease in the accruement of secondary mutations, presumably due to base damage, during carcinogenesis. This might be particularly true for tissues that undergo appreciable inflammatory responses and accompanying base damage that predispose to carcinogenesis, such as liver cirrhosis, hemochromatosis or pancreatitis (Hussain et al., 2000).
Interestingly, the human population exhibits a range of DNA repair capabilities. At the extreme low end of the spectrum is xeroderma pigmentosum severe phenotypic complementation groups A and G. Even some of the XP complementation groups are relatively modest in severity, e.g. XPE, within 2-fold of the normal range for NER (Abousekkhra and Wood, 1995). Importantly, even the `normal' population varies over about a 2-fold range of NER capacities (Parshad et al., 1996; Grossman, 1997) and, as XPE shows, even a 2-fold defect can predispose to carcinogenesis. It is likely that polymorphisms in DNA repair genes (Hemminki et al., 2001; Hu et al., 2001; Janssen et al., 2001), individual differences in regulation of DNA repair proteins, e.g. by phosphorylation (Ariza et al., 1996), and in regulation by protein–protein interaction, e.g. involving p53 and its effector proteins, contribute to DNA repair variation about the norm. Indeed, individual differences in p53 activity have been reported (Ljungman, 2001). p53 and DNA repair activities decline with the normal process of aging (Moriwaki et al., 1996; Goukassian et al., 2000) and p53 polymorphisms have been reported that may affect populations at large (Khaliq et al., 2000; Marin et al., 2000; Papadakis et al., 2000). One such polymorphism occurs at codon 72 (the normal Pro substituted by Arg), which may increase the risk of some cancers (Papadakis et al., 2000). Because p53 itself is complex, the contribution of the p53Arg versus p53Pro allele specifically to the DNA repair branch of the p53 pathway has not been explored. One approach may be to employ biological response modifiers, e.g. the Bowman–Birk protease inhibitor discussed above, to augment p53 and its associated DNA repair activities, in the population at large or in individuals carrying subtle defects in the p53 DNA repair pathways.
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Notes |
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1 To whom correspondence should be addressed at: Indiana University Cancer Center, 1044 West Walnut, R155, Indianapolis, IN 46202, USA
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References |
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TopAbstractHistorical significanceRole for p53 in...Role for p53 in...Relationship of p53, NER...Implications for...The DNA repair branch...References |
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Aboussekhra,A. and Wood,R.D. (1995) Detection of nucleotide excision repair incisions in human fibroblasts by immunostaining for PCNA. Exp. Cell Res., 221, 326–332.[Web of Science][Medline]
Adimoolam,S., Lin,C.X. and Ford,J.M. (2001) The p53-regulated cyclin-dependent kinase inhibitor p21 (Cip1, Waf1, Sdi1) is not required for global genomic and transcription-coupled nucleotide excision repair of UV-induced photoproducts. J. Biol. Chem., in press.
Ames,B. and Gold,L.S. (1997) The causes and prevention of cancer: gaining perspective. Environ. Health Perspect., 105 (suppl. 14), 865–873.
Amundson,S.A., Do,K.T., Shahab,S., Bittner,M., Meltzer,P., Trent,J. and Fornace,A.J.,Jr (2000) Identification of potential mRNA biomarkers in peripheral blood lymphocytes for human exposure to ionizing radiation. Radiat. Res., 154, 342–346.[Web of Science][Medline]
Ariza,R.R., Keyse,S.M., Moggs,J.G. and Wood,R.D. (1996) Reversible protein phosphorylation modulates nucleotide excision repair of damaged DNA by human cell extracts. Nucleic Acids Res., 24, 433–440.
Brown,J.M. and Wouters,B.G. (1999) Apoptosis, p53 and tumor cell sensitivity to anticancer agents. Cancer Res., 59, 1391–1399.
Carrier,F., Georgel,P., Pourquier,P., Blake,M., Kontny,H.U., Antinore,M.J., Gariboldi,M., Myers,T.G., Weinstein,J.N., Pommier,Y. and Fornace,A.J.,Jr (1999) Gadd45, a p53-responsive stress protein, modifies DNA accessibility on damaged chromatin. Mol. Cell. Biol., 19, 1673–1685.
Chang,D., Chen,F., Zhang,F., McKay,B.C. and Ljungman,M. (1999) Dose-dependent effects of DNA-damaging agents on p53-mediated cell cycle arrest. Cell Growth Differ., 10, 155–162.
Cheo,D.L., Ruven,H.J., Meira,L.B., Hammer,R.E., Burns,D.K., Tappe,N.J., van Zeeland,A.A., Mullenders,L.H. and Friedberg,E.C. (1997) Characterization of defective nucleotide excision repair in XPC mutant mice. Mutat. Res., 374, 1–9.[Web of Science][Medline]
Cheung,K.J., Mitchell,D., Lin,P. and Li,G. (2001) The tumor suppressor candidate p33(Ing1) mediates repair of UV-damaged DNA. Cancer Res., 61, 4974–4977.
Cistulli,C.A. and Kaufmann,W.K. (1998) p53-dependent signalling sustains DNA replication and enhances clonogenic survival in 254 nm ultraviolet-irradiated human fibroblasts. Cancer Res., 58, 1993–2002.
Dittmann,K.H., Gueven,N., Mayer,C., Ohnesheit,P., Zell,R., Begg,A.C. and Rodemann,H.P. (1998a) The presence of wild-type p53 is necessary for the radioprotective effect of the Bowman Birk proteinase inhibitor in normal fibroblasts. Radiat. Res., 150, 648–655.[Web of Science][Medline]
Dittmann,K.H., Gueven,N., Mayer,C. and Rodemann,H.P. (1998b) The radioprotective effect of BBI is associated with the activation of DNA repair-relevant genes. Int. J. Radiat. Biol., 74, 225–230.[Web of Science][Medline]
Dohn,M., Zhang,S. and Chen,X. (2001) P63alpha and deltaNp63alpha can induce cell cycle arrest and apoptosis and differentially regulate p53 target genes. Oncogene, 20, 3193–3205.[Web of Science][Medline]
El-Deiry,W.S., Kern,S.E., Pietenpol,J.A., Kinzler,K.W. and Vogelstein,B. (1992) Definition of a consensus binding site for p53. Nature Genet., 1, 45–49.[Web of Science][Medline]
El-Mahdy,M.A., Hamada,P.M., Wani,M.A., Zhu,Q. and Wani,A.A. (2000) P53 degradation by HPV16-E6 preferentially affects the removal of cyclobutane pyrimidine dimers from non-transcribed strand and sensitizes mammary epithelial cells to UV-irradiation. Mutat. Res., 459, 135–145.[Web of Science][Medline]
Fan,J. and Bertino,J.R. (1999) Modulation of cisplatinum cytotoxicity by p53: effect of p53-mediated apoptosis and DNA repair. Mol. Pharmacol., 56, 966–972.
Fan,S., Chang,J.K., Smith,M.L., Duba,D., Fornace,A.J.,Jr and O'Connor,P.M. (1997) Cells lacking CIP1/WAF1 genes exhibit preferential sensitivity to cisplatin and nitrogen mustard. Oncogene, 14, 2127–2136.[Web of Science][Medline]
Ford,J.M. and Hanawalt,P.C. (1995) Li-Fraumeni syndrome fibroblasts homozygous for p53 mutations are deficient in global DNA repair but exhibit normal transcription-coupled repair and enhanced UV-resistance. Proc. Natl Acad. Sci. USA, 92, 8876–8880.
Ford,J.M. and Hanawalt,P.C. (1997) Expression of wild-type p53 is required for efficient global genomic nucleotide excision repair in UV-irradiated human fibroblasts. J. Biol. Chem., 272, 28073–28080.
Ford,J.M., Baron,E.L. and Hanawalt,P.C. (1998) Human fibroblasts expressing the human papillomavirus E6 gene are deficient in global genomic nucleotide excision repair and sensitive to UV-irradiation. Cancer Res., 58, 599–603.
Friedberg,E.C., Walker,G.C. and Seide,W. (1995) DNA Repair and Mutagenesis. ASM Press, Washington, DC.
Ganesan,A.K., Hunt,J. and Hanawalt,P.C. (1999) Expression and nucleotide excision repair of a UV-irradiated reporter gene in unirradiated human cells. Mutat. Res., 433, 117–126.[Web of Science][Medline]
Goukassian,D., Gad,F., Yaar,M., Eller,M.S., Nehal,U.S. and Gilchrest,B.A. (2000) Mechanisms and implications of the age-associated decrease in DNA repair capacity. FASEB J., 14, 1325–1334.
Grossman,L. (1997) Epidemiology of ultraviolet-DNA repair capacity and human cancer. Environ. Health Perspect., 105, 927–930.
Harper,J.W., Adami,G.R., Wei,N., Keyomarsi,K. and Elledge,S.J. (1993) The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell, 75, 805–816.[Web of Science][Medline]
Havre,P.A., Yuan,J., Hedrick,L., Cho,K.R. and Glazer,P.M. (1995) P53 inactivation by HPV16-E6 results in increased mutagenesis in human cells. Cancer Res., 55, 4420–4424.
Hawkins,D.S., Demers,G.W. and Galloway,D.A. (1996) Inactivation of p53 enhances sensitivity to multiple chemotherapeutic agents. Cancer Res., 56, 892–898.
Hemminki,K., Xu,G., Angelini,S., Snellman,E., Jansen,C.T., Lambert,B. and Hou,S.M. (2001) XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ. Carcinogenesis, 22, 1185–1188.
Hirose,Y., Berger,M.S. and Pieper,R.O. (2001) P53 affects both the duration of G2/M arrest and the fate of temozolomide-treated human glioblastoma cells. Cancer Res., 61, 1957–1963.
Hollander,M.C., Anver,M., Kim,K. and Fornace,A.J.,Jr (2001) DMBA carcinogenesis in gadd45-null mice is associated with decreased DNA repair and increased mutation frequency. Cancer Res., 61, 2487–2491.
Hu,J.J., Smith,T.R., Miller,M.S., Mohrenweiser,H.W., Golden,A. and Case,L.D. (2001) Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis, 22, 917–922.
Hussain,S.P., Raja,K., Amstad,P.A., Sawyer,M., Trudel,L., Wogan,G., Hofseth,L., Shields,P., Billiar,T., Trautwein,C., Hohler,T., Galle,P., Phillips,D., Markin,R., Marrogi,A. and Harris,C.C. (2000) Increased p53 mutation load in nontumorous human liver of Wilson disease and hemochromotosis: oxyradical overload disease. Proc. Natl Acad. Sci. USA, 97, 12770–12775.
Hwang,B.J., Ford,J.M., Hanawalt,P.C. and Chu,G. (1999) Expression of the p48xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair. Proc. Natl Acad. Sci. USA, 96, 424–428.
Janssen,K., Schlink,K., Gotte,W., Hippler,B., Kaina,B. and Oesch,F. (2001) DNA repair activity of 8-oxoguanine DNA glycosylase (OGG1) in human lymphocytes is not dependent on genetic polymorphism Ser(326)/Cys(326). Mutat. Res., 486, 207–216.[Web of Science][Medline]
Jin,S., Zhao,H., Fan,F., Blanck,P., Colchagie,A.B., Fornace,A.J. and Zhan,Q. (2000) BRCA1 activation of the GADD45 promoter. J. Biol. Chem., 19, 4050–4057.
Jones,C.B., Clements,M.K., Redkar,A. and Daoud,S.S. (2000) UCN01 and camptothecin induce DNA double-strand breaks in p53 mutant tumor cells, but not in normal or p53 negative epithelial cells. Int. J. Oncol., 17, 1043–1051.[Web of Science][Medline]
Kastan,M.B., Zhan,Q., el-Deiry,W.S., Carrier,F., Jacks,T., Walsh,W.V., Plunkett,B.S., Vogelstein,B. and Fornace,A.J.,Jr (1992) A mammalian cell cycle checkpoint pathway utilizing p53 and Gadd45 is defective in ataxia telangiectasia. Cell, 71, 587–597.[Web of Science][Medline]
Khaliq,S., Hameed,A., Khaliq,T., Ayub,Q., Qamar,R., Mohyuddin,A., Mazhar,K. and Qasim-Mehdi,S. (2000) P53 mutations, polymorphisms and haplotypes in Pakistani ethnic groups and breast cancer patients. Genet. Test., 4, 23–29.[Web of Science][Medline]
Kuraoka,I., Bender,C., Romieu,A., Cadet,J., Wood,R.D. and Lindahl,T. (2000) Removal of oxygen free radical-induced cyclodeoxynucleotides from DNA by the nucleotide excision repair pathway in human cells. Proc. Natl Acad. Sci. USA, 97, 3832–3837.
Leveillard,T., Andera,L., Bissonnette,N., Schaffer,L., Bracco,L., Egly,J.M. and Wasylyk,B. (1996) Functional interactions between p53 and the TFIIH complex are affected by tumour-associated mutations. EMBO J., 15, 1615–1624.[Web of Science][Medline]
Levine,A.J. (1997). P53, the cellular gatekeeper for growth and division. Cell, 88, 323–331.[Web of Science][Medline]
Li,G. and Ho,V.C. (1998) P53-dependent DNA repair and apoptosis respond differently to high and low-dose ultraviolet radiation. Br. J. Dermatol., 139, 3–10.
Ljungman,M. (2001) Individual variation in p53 responsiveness. J. Natl Cancer Inst., 93, 82–83.
Lloyd,D.R. and Hanawalt,P.C. (2000) P53-dependent global genomic repair of benzo[a]pyrene-7,8-diol-9,10-epoxide adducts in human cells. Cancer Res., 60, 517–521.
Marin,M.C., Jost,C.A., Brooks,L.A., Irwin,M.S., O'Nions,J., Tidy,J.A., James,N., McGregor,J.M., Harwood,C.A., Yulug,I.G., Vousden,K.H., Allday,M.J., Gusterson,B., Ikawa,S., Hinds,P.W., Crook,T. and Kaelin,W.G.,Jr (2000) A common polymorphism acts as an intragenic modifier of mutant p53 behavior. Nature Genet., 25, 47–54.[Web of Science][Medline]
Matsumoto,Y., Kim,K., Hurwitz,J., Gary,R., Levin,D.S., Tomkinson,A.E. and Park,M.S. (1999) Reconstitution of PCNA-dependent repair of apurinic/apyrimidinic sites with purified human proteins. J. Biol. Chem., 274, 33703–33708.
McDonald,E.R., Wu,G.S., Waldman,T. and El-Deiry,W.S. (1996) Repair defect in p21Waf1/Cip1–/– human cancer cells. Cancer Res., 56, 2250–2255.
McKay,B.C., Chen,F., Perumalswami,C.R., Zhang,F. and Ljungman,M. (2000) The tumor suppressor p53 can both stimulate and inhibit ultraviolet-light-induced apoptosis. Mol. Biol. Cell, 11, 2543–2551.
Meyer,K.M., Hess,S.M., Tlsty,T.D. and Leadon,S.A. (1999) Human mammary epithelial cells exhibit a differential p53-mediated response following exposure to ionizing radiation or UV light. Oncogene, 18, 5795–5805.[Web of Science][Medline]
Moriwaki,S., Ray,S., Tarone,R.E., Kraemer,K.H. and Grossman,L. (1996) The effect of donor age on the processing of UV-damaged DNA by cultured human cells. Reduced DNA repair capacity and increased DNA mutability. Mutat. Res., 364, 117–123.[Web of Science][Medline]
Nichols,K.E., Malkin,D., Garber,J.E., Fraumeni,J.F. and Li,F.P. (2001) Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiol. Biomarkers Prev., 10, 83–87.
Offer,H., Zurer,I., Banfalvi,G., Reha'k,M., Falcovitz,A., Milyausky,M., Goldfinger,N. and Rotter,V. (2001) P53 modulates base excision repair activity in cell cycle specific manner after genotoxic stress. Cancer Res., 61, 88–96.
Papadakis,E.N., Dokianakis,D.N. and Spandidos,D.A. (2000) P53 codon 72 polymorphism as a risk factor in the development of breast cancer. Mol. Cell. Biol. Res. Commun., 3, 389–392.[Medline]
Parshad,R., Price,F.M., Bohr,V.A., Cowan,K.H., Zujewski,J.A. and Sanford,K. (1996) Deficient DNA repair capacity, a predisposing factor in cancer. Br. J. Cancer, 74, 1–5.[Web of Science][Medline]
Pratesi,G., Perego,P., Polizzi,D., Righetti,S.C., Supino,R., Caserini,C., Manzotti,C., Giuliani,F.C., Pezzoni,G., Tognella,S., Spinelli,S., Farrell,N. and Zunino,F. (1999) A novel charged trinuclear platinum complex effective against cisplatin-resistant tumours: hypersensitivity of p53-mutant human tumour xenografts. Br. J. Cancer, 80, 1912–1919.[Web of Science][Medline]
Seo,Y.R., Chen,E. and Smith,M.L. (2001a) Sensitivity of p53-deficient cells to oxaliplatin and thio-TEPA (N,N',N''-triethylenethiophosphoramide). Breast Cancer Res. Treat., in press.
Seo,Y.R., Limp-Foster,M., Kelley,M.R. and Smith,M.L. (2001b) Implication of p53 in base excision DNA repair: in vivo evidence. Oncogene, in press.
Sheikh,M.S., Chen,Y.Q., Smith,M.L. and Fornace,A.J.,Jr (1997) Role of p21Waf1/Cip1/Sdi1 in cell death and DNA repair as studied using a tetracycline-inducible system in p53-deficient cells. Oncogene, 14, 1875–1882.[Web of Science][Medline]
Smith,M.L. and Fornace,A.J.,Jr (1997) P53-mediated protective responses to UV-irradiation. Proc. Natl Acad. Sci. USA, 94, 12255–12257.
Smith,M.L., Chen,I.T., Zhan,Q., O'Connor,P.M. and Fornace,A.J.,Jr. (1995) Involvement of the p53 tumor suppressor in repair of UV-type DNA damage. Oncogene, 10, 1053–1059.[Web of Science][Medline]
Smith,M.L., Ford,J.M., Hollander,M.C., Bortnick,R.A., Amundson,S.A., Seo,Y.R., Deng,C., Hanawalt,P.C. and Fornace,A.J.,Jr (2000) P53-mediated DNA repair responses to UV-radiation: studies of mouse cells lacking p53, p21 and/or gadd45 genes. Mol. Cell. Biol., 20, 3705–3714.
Stivala,L.A., Riva,F., Cazzalini,O., Savio,M. and Prosperi,E. (2001) P21(waf1/cip1)-null human fibroblasts are deficient in nucleotide excision repair downstream of the recruitment of PCNA to repair sites. Oncogene, 20, 563–570.[Web of Science][Medline]
Stucki,M., Pascucci,B., Parlanti,E., Fortini,P., Wilson,S.H., Hubscher,U. and Dogliotti,E. (1998) Mammalian base excision repair by DNA polymerases delta and epsilon. Oncogene, 17, 835–843.[Web of Science][Medline]
Tanaka,H., Arakawa,H., Yamaguchi,T., Shiraishi,K., Fukuda,S., Matsui,K., Takei,Y. and Nakamura,Y. (2000) A ribonucleotide reductase gene involved in p53-dependent cell cycle checkpoint for DNA damage. Nature, 404, 42–49.[Medline]
Tokino,T., Thiagalingham,S., El-Deiry,W.S., Waldman,T., Kinzler,K.W. and Vogelstein,B. (1994) P53 tagged sites from human genomic DNA. Hum. Mol. Genet., 3, 1537–1542.
Vikhanskaya,F., Marchini,S., Maranese,M., Galliera,E. and Broggini,M. (2001) P73a overexpression is associated with resistence to treatment with DNA-damaging agents in a human ovarian cancer cell line. Cancer Res., 61, 935–938.
Wang,Q., Fan,S., Eastman,A., Worland,P.J., Sausville,E.A. and O'Connor,P.M. (1996) UCN-01: a potent abrogator of G2 checkpoint function in cancer cells with disrupted p53. J. Natl Cancer Inst., 88, 956–965.
Wang,X.W., Yeh,H., Schaffer,L., Roy,R., Moncollin,V., Egly,J.M., Wang,Z., Friedberg,E.C., Evans,M.K., Taffe,B.G., Bohr,V.A. and Harris,C.C. (1995) p53 modulation of TFIIH-associated nucleotide excision repair activity. Nature Genet., 10, 188–195.[Web of Science][Medline]
Xu,G.W., Nutt,C.L., Zlatescu,M.C., Keeney,M., Chen-Yee,I. and Cairncross,J.G. (2001) Inactivation of p53 sensitizes U87MG glioma cells to 1,3-bis(2-chloroethyl)-1-nitrosourea. Cancer Res., 61, 4155–4159.
Xu,Y., Hansen,W.K., Rosenquist,T.A., Williams,D.A., Limp-Foster,M. and Kelley,M.R. (2001) Protection of mammalian cells against chemotherapeutic agents thiotepa, 1,3-N,N'-bis(2-chloroethyl)-N-nitrosourea and mafosfamide using the DNA base excision repair genes Fpg and alpha-hOgg1: implications for protective gene therapy applications. J. Pharmacol. Exp. Ther., 296, 825–831.
Yamane,K., Katayama,E. and Tsuruo,T. (2001) P53 contains a DNA break-binding motif similar to the functional part of BRCT-related region of Rb. Oncogene, 20, 2859–2867.[Web of Science][Medline]
Yuan,J., Yeasky,T.M., Havre,P.A. and Glazer,P.M. (1995) Induction of p53 in mouse cells decreases mutagenesis by UV-radiation. Carcinogenesis, 10, 2295–2300.
Zhan,Q., Carrier,F. and Fornace,A.J.,Jr (1993) Induction of cellular p53 activity by DNA-damaging agents and growth arrest. Mol. Cell. Biol., 13, 4242–4250.
Zhan,Q., Fan,S., Smith,M.L., Bae,I., Yu,K., Alamo,I., O'Connor,P.M. and Fornace,A.J.,Jr (1996) Abrogation of p53 function affects gadd gene responses to DNA base-damaging agents and starvation. DNA Cell Biol., 15, 805–815.[Web of Science][Medline]
Zhou,J., Ahn,J., Wilson,S.H. and Prives,C. (2001) A role for p53 in base excision repair. EMBO J., 20, 914–923.[Web of Science][Medline]
Zhu,Q., Wani,M.A., El-Mahdy,M. and Wani,A.A. (2000) Decreased DNA repair efficiency by loss or disruption of p53 function preferentially affects removal of cyclobutane pyrimidine dimers from the non-transcribed strand and slow repair sites in transcribed strand. J. Biol. Chem., 275, 11492–11497.
Received on August 3, 2001; revised on October 16, 2001; accepted on October 19, 2001.
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