Mutagenesis Advance Access originally published online on June 14, 2006
Mutagenesis 2006 21(4):219-224; doi:10.1093/mutage/gel024
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TDP1-dependent DNA single-strand break repair and neurodegeneration
1 Genome Damage and Stability Centre, University of Sussex Falmer, Brighton BN1 9RQ, UK 2 Biochemistry Department, Faculty of Pharmacy, Ain Shams University PO Box 11566, Cairo, Egypt
DNA single-strand breaks (SSBs) are the commonest DNA lesions that arise spontaneously in living cells. Cells employ efficient processes for the rapid repair of these breaks and defects in these processes appear to preferentially impact on the nervous system, causing human ataxia. Spinocerebellar ataxia with axonal neuropathy (SCAN1) is a human disease that is associated with a defect in repairing certain types of SSBs. Although it is a rare neurodegenerative disease, understanding the molecular basis of SCAN1 will lead to better understanding of the mechanisms that underpin not only neurodegeneration but also cancer.
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DNA single-strand breaks and human ataxia |
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DNA is under continuous threat and thousands of DNA single-strand breaks (SSBs) arise in each cell per day (1
). SSBs can arise either directly (e.g. from attack of deoxyribose by reactive oxygen species) or indirectly via enzymatic cleavage of the phosphodiester backbone during DNA base excision repair (2). Cells have employed different mechanisms to repair DNA SSBs, which are collectively termed DNA SSB repair (SSBR) (3,4). Defects in the repair of, or response to, DNA damage have been associated with many human disorders such as cancer, immunodeficiency and neurodegeneration. Recent data suggest that defects in the repair or response to DNA SSBs may have particular impact on the nervous system and are associated with human ataxia (5–7).
Ataxia is a neurological dysfunction of motor coordination that can affect gait, speech, gaze and balance (8). The first autosomal dominant gene for a hereditary ataxia, spinocerebellar ataxia (SCA1), was identified in 1993 (9). Autosomal dominant SCAs are caused mainly by a toxic gain-of-function mutations arising from an expansion of CAG-triplet repeats in the coding region of the disease gene, which results in the production of a mutant protein with an abnormal polyglutamine stretch (10). In contrast, autosomal recessive ataxias are often caused by loss-of-function mutations that result in perturbations in the normal control of, or response to, oxidative stress and/or DNA damage (8,11–14). Clinically, autosomal recessive SCAs are characterized by cerebellar ataxia and progressive degeneration of the cerebellum and spinocerebellar tract (11). Disorders in DNA repair typically cause additional symptoms such as mental retardation, photosensitivity, immunodeficiency and neoplasia (15,16). For example, two spinocerebellar ataxias with defects in response to DNA double-strand breaks (DSBs), ataxia telangiectasia (AT) and ataxia telangiectasia-like disorder (ATLD), also exhibit radiosensitivity, immunodeficiency and chromosomal instability (16–18).
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Spinocerebellar ataxia with axonal neuropathy (SCAN1) |
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TopDNA single-strand breaks and...Spinocerebellar ataxia with...Tyrosyl-DNA phosphodiesterase...TDP1 is a component...Why does mutation of...Conclusion and future directionsReferences |
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Recently Takashima et al. (7
) identified an autosomal recessive ataxia, which they named spinocerebellar ataxia with axonal neuropathy (SCAN1). Interestingly, the SCAN1 phenotype lacks chromosomal instability and cancer predisposition, and symptoms appear to be restricted to the nervous system. SCAN1 is associated with a mutation in tyrosyl-DNA phosphodiesterase 1 (TDP1), a protein that is primarily involved in the repair of DNA strand breaks created by topoisomerase 1 (Top1). Top1 relaxes superhelical tension in DNA and during its normal catalytic cycle generates a reversible and transient intermediate known as the Top1 cleavage complex, in which Top1 is covalently attached via a tyrosyl residue (human Tyr723) to the 3'-terminus of a single-stranded nick (19). Following release of torsional stress, Top1 reseals the nick and restores the integrity of the double helix (20). The rate of religation is normally much faster than the rate of cleavage and thus the steady-state concentration of these intermediates is very low (20,21). However, under certain circumstances, Top1 cleavage complexes may become irreversible, which is probably due to misalignment of the 5'-hydroxyl that is no longer able to act as a nucleophile in the religation reaction (20). Consequently, this irreversible ‘abortive’ Top1-associated DNA break requires a DNA repair process for its removal. For example, Top1 cleavage complexes can be converted into abortive Top1-associated DNA DSBs by collision with a replication fork (22–26). In addition, collision with the transcription machinery converts Top1 cleavage complexes into abortive Top1-associated DNA SSBs, and occasionally abortive Top1-associated DSBs if two Top1 cleavage complexes are closely spaced on opposite strands of DNA (27–29). Finally, some mutagenic DNA adducts (30–32) and endogenous DNA lesions such as abasic sites, nicks, gaps and DNA secondary structures can convert Top1 cleavage complexes into abortive Top1-associated DNA SSBs (Figure 1) (33–37).
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Tyrosyl-DNA phosphodiesterase (TDP1) |
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In 1996, Nash and colleagues (38
) employed a single-stranded DNA oligonucleotide linked to a tyrosine residue via a 3'-phosphoryl group, mimicking an abortive Top1-associated DNA strand break, to identify an activity in Saccharomyces cerevisiae extract that was able to remove Top1 from the 3'-terminus of DNA. They named the activity tyrosyl-DNA phosphodiesterase 1 (Tdp1), and gene encoding this activity was subsequently cloned (39). TDP1 is highly conserved in eukaryotes, with identifiable orthologs in a wide variety of animals, including humans (20,39–42). Sequence analysis of S.cerevisiae Tdp1 (39,43) and the crystal structure of human TDP1 (44,45) reveal it to be a member of the phospholipase D (PLD) superfamily. These enzymes contain two copies of a highly conserved sequence (HXK(X)4D(X)6GSXN), known as HKD motif (43) and catalyse phosphoryl transfer reactions. Despite lacking the aspartate conserved in other HKD motifs, the crystal structure of human TDP1 has shown that both histidine and lysine residues of the HKD motifs are clustered in the active centre of the enzyme (42,44,45).
Our initial understanding of the role for TDP1 in DNA repair came from studies conducted in budding yeast. Yeast Tdp1 provides one of several potentially redundant mechanisms for removing Top1 peptide from a DSB created by collision of Top1 cleavage complexes with DNA replication forks (46–48). Once Top1 peptide has been removed, the DSB is then channelled into the homologous recombination (HR) pathway for DSB repair (DSBR) (47,48). Tdp1 in yeast appears to operate in conjunction with HR to repair Top1-associated DSBs, because mutation of Tdp1 is epistatic to mutations in critical components of the HR pathway, such as Rad52 (47,48). As in yeast, it is possible that human TDP1 plays a role during DNA replication. The cytotoxic effect of the Top1-specific inhibitor camptothecin (CPT) is S-phase specific in most wild-type mammalian cell lines examined (49–52) and is ablated by co-incubation with aphidicolin, an inhibitor of DNA replication (23,25). Thus, ongoing replication forks appear to be required to convert Top1 cleavage complexes into cytotoxic lesions, in wild-type proliferating cells at least (53–60). It is therefore plausible that TDP1 inhibitors may enhance the anti-cancer activity of Top1 inhibitors and act as anti-proliferative agents (61). Consistent with a possible role for human TDP1 during replication, lymphoblastoid cell lines (LCLs) from affected SCAN1 individuals appear to show more late S-phase arrest than normal cells following CPT treatment (62). This could reflect a direct role for TDP1 during replication or an accumulation of un-repaired SSBs that are consequently converted into DSBs by collision with replication forks.
Nevertheless, a role for TDP1 during DNA replication is unlikely to account for the SCAN1 pathology, which appears to be restricted to post-mitotic neurons and lacks any obvious genetic instability or cancer. To address this question, we recently examined the ability of SCAN1 LCLs to repair CPT-induced DNA strand breaks using the alkaline comet assay. SCAN1 cells accumulated more total DNA strand breaks than did normal cells during a 1 h incubation with CPT. These breaks failed to decline in SCAN1 cells during a subsequent incubation in CPT-free medium and approximately half were replication-independent and primarily comprised of DNA SSBs. The DNA breaks that accumulate in SCAN1 may arise from a stalled Top1 or could reflect a stalled TDP1 attempting to repair an abortive Top1 break. The latter possibility arose from the recent observation that TDP1 mutation in SCAN1 causes the accumulation of the TDP1–DNA covalent reaction intermediate (62). It is worth noting, however, that accumulation of CPT-induced DNA breaks is also observed in neural cells lacking TDP1 (El-Khamisy, S.F. and McKinnon, P.J. unpublished observations).
SCAN1 cells were also less able than normal cells to repair oxidative DNA SSBs induced by H2O2, though the defect was not as pronounced as for CPT (63). This could reflect a direct requirement for TDP1 in processing oxidative DNA breaks. It has been shown that TDP1 can remove glycolate from 3'-phosphoglycolate termini of DSBs (64) and a variety of other 3'-adducts from DNA (65). In addition, yeast expressing an active site mutant of Tdp1 (His182Ala) are hypersensitive to bleomycin, a radiomimetic agent which generates DNA breaks that are almost exclusively terminated with 3'-phosphoglycolate (66). Moreover, in vitro assays have recently shown that SCAN1 cell extracts lack any detectable processing of 3'-phosphoglycolate at single-stranded oligomers or at 3'-overhangs of DSBs (67). However, the use of a substrate with a single-stranded gap that harbours 3'-phosphoglycolate revealed APE1 as the major 3'-phosphoglycolate-processing activity in human cell extracts (68). This suggests that TDP1 may not be a major contributor in removing 3'-phosphoglycolate at sites of SSBs. An alternative explanation for the reduced repair of oxidative SSBs in SCAN1 cells would be an increased formation of Top1-associated SSBs following treatment with H2O2. Indeed, the presence of nicks (34), abasic sites (37), modified bases (69,70) and modified sugars (71) has been shown to stabilize and/or induce Top1 cleavage complexes. Consistent with this, Top1-deficient P388/CPT45 murine leukaemia cells are more resistant to H2O2 than Top1-proficient parental cells (72). In addition, over-expression of Top1 in yeast confers sensitivity to H2O2 and top1-mutant strains are more resistant to H2O2 than their isogenic wild-type strains (72). Finally, studies employing HeLa cells have confirmed that H2O2 does indeed induce Top1-DNA cross-links (72).
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TDP1 is a component of the SSBR machinery |
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Yeast two-hybrid and co-immunoprecipitation experiments have provided evidence for a direct interaction between TDP1 and DNA ligase III
, a component of the DNA SSBR machinery (63). In agreement with this, it has been shown that TDP1 co-immunoprecipitates with XRCC1 in rodent cell extract (73). The interaction between TDP1 and DNA ligase III is mediated by the N-terminal domain of TDP1, a region that is poorly conserved or absent from Tdp1 of lower eukaryotes (43,63). Budding yeast lack orthologs of various components of SSBR machinery found in mammals, including XRCC1 and DNA ligase III. Therefore it seems likely that the N-terminal domain of human TDP1 may have evolved to couple this enzyme to the SSBR machinery, through an interaction with DNA ligase III. Interestingly, it has been shown that the global SSBR process that operates throughout interphase requires the BRCTII domain of XRCC1, a domain that mediates the interaction with DNA ligase III (74,75). The observation that TDP1 interacts with DNA ligase III and that TDP1 mutation is manifested in non-proliferating cells is thus consistent with a particular importance of the SSBR process in post-mitotic tissue.
The current models of SSBR suggest sequential recruitment of the enzymes such that DNA repair-intermediates are passed from one enzyme to the other in a molecular relay (76,77). However, at least some of the XRCC1 appear to be present in pre-formed multi-protein complexes (78–81). TDP1 appears to be constitutively associated with SSBR machinery, though it is unclear whether these interactions are occurring in response to ‘endogenous’ levels of DNA damage or are truly constitutive.
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Why does mutation of TDP1 cause neurodegeneration? |
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The brain encounters high levels of oxidative stress as it consumes
20% of the inhaled oxygen and possesses low levels of antioxidant enzymes (82). The formation of high levels of oxidative lesions may directly require TDP1-SSBR for their removal and may also trap more Top1, which in turn increases the demand for TDP1-SSBR. In addition, there is a high level of transcriptional demand in post-mitotic neurons. For example, cortical neurons incorporate 5.5-fold more 3H-uridine than astrocytes (83) and possess twice the number of transcription initiation sites as compared to glial cells (84–86). It is thus possible that the high transcriptional activity in neurons may increase the frequency of collision between RNA polymerases and un-repaired SSBs, which can consequently block elongating RNA polymerases and compromise cellular function. Consistent with this, SCAN1 cells were unable to recover transcription following CPT treatment (63). The absence of any obvious genetic instability or cancer in SCAN1 may reflect the ability of homologous recombination (HR) repair to compensate for defective TDP1-SSBR by removing un-repaired SSBs during DNA replication. Consistent with this, HR is selectively elevated in SCAN1 cells as indicated by an increased frequency of ‘spontaneous’ and ‘CPT-induced’ sister chromatid exchanges (63). Thus, it seems possible that HR can fulfil a back-up role in the absence of TDP1-dependent SSBR, allowing proliferating SCAN1 cells to tolerate un-repaired SSBs, at physiological levels of DNA damage at least (Figure 2). If this is true, then why are other predominantly non-cycling tissues not affected in SCAN1? The high levels of oxidative stress and transcriptional demand in post-mitotic neurons, coupled to the limited regenerative capacity of the nervous system, may render this tissue particularly susceptible to defects in TDP1-SSBR and the possible cell loss. This is in contrast to cell loss from tissues with greater regenerative capacity that may be better tolerated. For example, myocytes and adipocytes are also terminally differentiated, but can be replaced by precursor cells (87–89).
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Conclusion and future directions |
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Whereas a great insight into the molecular role of TDP1 has come from studies with yeast, SCAN1 cells and recombinant TDP1, there is still much that is unresolved. To date, most studies have utilized transformed cells, but a demonstrated role for TDP1 in primary neuronal cells is currently lacking. Accordingly, we are only beginning to understand the possible impact of un-repaired SSBs on post-mitotic neuronal cells and many issues remain. For example, why might TDP1 mutation selectively affect certain neuronal tissue such as the cerebellum? Why is the developing brain resistant to TDP1 mutation and the disease has late onset? Does mutation in other components of SSBR machinery such as DNA ligase III
and XRCC1 also impact on the nervous system? The development of animal models and conditional knockout alleles will be an important tool to address these questions and to enhance our understanding of the relationship between SSBR and neurodegeneration.
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Acknowledgments |
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We apologize to colleagues whose primary research papers may not have been cited due to space constraints. This work was supported by an MRC program grant to K.W.C. and an ORS to S.F.E.-K.
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Notes |
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*To whom correspondence should be addressed. Tel: +1273 877511; Fax: +1273 678121; Email: smfame20{at}sussex.ac.uk
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References |
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-
1. Lindahl T. (1993) Instability and decay of the primary structure of DNA. Nature 362:709–715.[CrossRef][Medline]
2. Beckman K.B. and Ames B.N. (1997) Oxidative decay of DNA. J. Biol. Chem. 272:19633–19636.
3. Thompson L.H. and West M.G. (2000) XRCC1 keeps DNA from getting stranded. Mutat. Res. 459:1–18.[ISI][Medline]
4. Caldecott K.W. (2004) DNA single-strand breaks and neurodegeneration. DNA Repair (Amst.) 3:875–882.[CrossRef][Medline]
5. Date H., Onodera O., Tanaka H., et al. (2001) Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. Nat. Genet. 29:184–188.[CrossRef][ISI][Medline]
6. Moreira M.C., Barbot C., Tachi N., Kozuka N., Mendonca P., Barros J., Coutinho P., Sequeiros J., Koenig M. (2001) Homozygosity mapping of Portuguese and Japanese forms of ataxia-oculomotor apraxia to 9p13, and evidence for genetic heterogeneity. Am. J. Hum. Genet. 68:501–508.[CrossRef][ISI][Medline]
7. Takashima H., Boerkoel F.C., John J., et al. (2002) Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy. Nat. Genet. 32:267–272.[CrossRef][ISI][Medline]
8. Taroni F. and DiDonato S. (2004) Pathways to motor incoordination: the inherited ataxias. Nat. Rev. Neurosci. 5:641–655.[ISI][Medline]
9. Orr H.T., Chung Y.M., Banfi S., Kwiatkowski J.T. Jr, Servadio A., Beaudet L.A., McCall E.A., Duvick A.L., Ranum P.L., Zoghbi H.Y. (1993) Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat. Genet. 4:221–226.[CrossRef][ISI][Medline]
10. Abou-Sleymane G., Chalmel F., Helmlinger D., et al. (2006) Polyglutamine expansion causes neurodegeneration by altering the neuronal differentiation program. Hum. Mol. Genet. 15:691–703.
11. Di Donato S., Gellera C., Mariotti C. (2001) The complex clinical and genetic classification of inherited ataxias. II. Autosomal recessive ataxias. Neurol. Sci. 22:219–228.[CrossRef][ISI][Medline]
12. Gakh O., Park S., Liu G., Macomber L., Imlay A.J., Ferreira C.G., Isaya G. (2006) Mitochondrial iron detoxification is a primary function of frataxin that limits oxidative damage and preserves cell longevity. Hum. Mol. Genet. 15:467–479.
13. Thierbach R., Schulz J.T., Isken F., et al. (2005) Targeted disruption of hepatic frataxin expression causes impaired mitochondrial function, decreased life span and tumor growth in mice. Hum. Mol. Genet. 14:3857–3864.
14. Calabrese V., Lodi R., Tonon C., D'Agata V., Sapienza M., Scapagnini G., Mangiameli A., Pennisi G., Stella M.A., Butterfield D.A. (2005) Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich's ataxia. J. Neurol. Sci. 233:145–1 62.[CrossRef][ISI][Medline]
15. de Boer J. and Hoeijmakers J.H. (2000) Nucleotide excision repair and human syndromes. Carcinogenesis 21:453–460.
16. O'Driscoll M. and Jeggo P.A. (2006) The role of double-strand break repair—insights from human genetics. Nat. Rev. Genet. 7:45–54.[CrossRef][ISI][Medline]
17. Taylor A.M., Groom A., Byrd P.J. (2004) Ataxia-telangiectasia-like disorder (ATLD)-its clinical presentation and molecular basis. DNA Repair (Amst.) 3:1219–1225.[CrossRef][Medline]
18. Stewart G.S., Maser S.R., Stankovic T., Bressan A.D., Kaplan I.M., Jaspers G.N., Raams A., Byrd J.P., Petrini H.J., Taylor A.M. (1999) The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell 99:577–587.[CrossRef][ISI][Medline]
19. Wang J.C. (2002) Cellular roles of DNA topoisomerases: a molecular perspective. Nat. Rev. Mol. Cell. Biol. 3:430–440.[CrossRef][ISI][Medline]
20. Pommier Y., Redon C., Rao A.V., et al. (2003) Repair of and checkpoint response to topoisomerase I-mediated DNA damage. Mutat. Res. 532:173–203.[ISI][Medline]
21. Rideout M.C., Raymond C.A., Burgin B.A. Jr. (2004) Design and synthesis of fluorescent substrates for human tyrosyl-DNA phosphodiesterase I. Nucleic Acids Res. 32:4657–4664.
22. Avemann K., Knippers R., Koller T., Sogo J.M. (1988) Camptothecin, a specific inhibitor of type I DNA topoisomerase, induces DNA breakage at replication forks. Mol. Cell. Biol. 8:3026–3034.
23. Holm C., Covey M.J., Kerrigan D., Pommier Y. (1989) Differential requirement of DNA replication for the cytotoxicity of DNA topoisomerase I and II inhibitors in Chinese hamster DC3F cells. Cancer Res. 49:6365–6368.
24. Hsiang Y.H., Lihou G.M., Liu L.F. (1989) Arrest of replication forks by drug-stabilized topoisomerase I-DNA cleavable complexes as a mechanism of cell killing by camptothecin. Cancer Res. 49:5077–5082.
25. Ryan A.J., Squires S., Strutt L.H., Johnson R.T. (1991) Camptothecin cytotoxicity in mammalian cells is associated with the induction of persistent double strand breaks in replicating DNA. Nucleic Acids Res. 19:3295–3300.
26. Strumberg D., Pilon A.A., Smith M., Hickey R., Malkas L., Pommier Y. (2000) Conversion of topoisomerase I cleavage complexes on the leading strand of ribosomal DNA into 5'-phosphorylated DNA double-strand breaks by replication runoff. Mol. Cell. Biol. 20:3977–3987.
27. Bendixen C., Thomsen B., Alsner J., Westergaard O. (1990) Camptothecin-stabilized topoisomerase I-DNA adducts cause premature termination of transcription. Biochemistry 29:5613–5619.[CrossRef][Medline]
28. Wu J. and Liu L.F. (1997) Processing of topoisomerase I cleavable complexes into DNA damage by transcription. Nucleic Acids Res. 25:4181–4186.
29. Kroeger P.E. and Rowe T.C. (1989) Interaction of topoisomerase 1 with the transcribed region of the Drosophila HSP 70 heat shock gene. Nucleic Acids Res. 17:8495–8509.
30. Pourquier P., Bjornsti A.M., Pommier Y. (1998) Induction of topoisomerase I cleavage complexes by the vinyl chloride adduct 1,N6-ethenoadenine. J. Biol. Chem. 273:27245–27249.
31. Pommier Y., Kohlhagen G., Pourquier P., Sayer M.J., Kroth H., Jerina D.M. (2000) Benzo[a]pyrene diol epoxide adducts in DNA are potent suppressors of a normal topoisomerase I cleavage site and powerful inducers of other topoisomerase I cleavages. Proc. Natl Acad. Sci. USA 97:2040–2045.
32. Pourquier P., Waltman L.J., Urasaki Y., Loktionova A.N., Pegg E.A., Nitiss L.J., Pommier Y. (2001) Topoisomerase I-mediated cytotoxicity of N-methyl-N'-nitro-N-nitrosoguanidine: trapping of topoisomerase I by the O6-methylguanine. Cancer Res. 61:53–58.
33. Pommier Y., Laco S.G., Kohlhagen G., Sayer M.J., Kroth H., Jerina D.M. (2000) Position-specific trapping of topoisomerase I-DNA cleavage complexes by intercalated benzo[a]-pyrene diol epoxide adducts at the 6-amino group of adenine. Proc. Natl Acad. Sci. USA 97:10739–10744.
34. Pourquier P., Pilon A.A., Kohlhagen G., Mazumder A., Sharma A., Pommier Y. (1997) Trapping of mammalian topoisomerase I and recombinations induced by damaged DNA containing nicks or gaps. Importance of DNA end phosphorylation and camptothecin effects. J. Biol. Chem. 272:26441–26447.
35. Christiansen K. and Westergaard O. (1999) Mapping of eukaryotic DNA topoisomerase I catalyzed cleavage without concomitant religation in the vicinity of DNA structural anomalies. Biochim. Biophys. Acta 1489:249–262.[Medline]
36. Lanza A., Tornaletti S., Rodolfo C., Scanavini C.M., Pedrini A.M. (1996) Human DNA topoisomerase I-mediated cleavages stimulated by ultraviolet light-induced DNA damage. J. Biol. Chem. 271:6978–6986.
37. Pourquier P., Ueng M.L., Kohlhagen G., Mazumder A., Gupta M., Kohn W.K., Pommier Y. (1997) Effects of uracil incorporation, DNA mismatches, and abasic sites on cleavage and religation activities of mammalian topoisomerase I. J. Biol. Chem. 272:7792–7796.
38. Yang S.W., Burgin B.A. Jr, Huizenga N.B., Robertson A.C., Yao C.K., Nash H.A. (1996) A eukaryotic enzyme that can disjoin dead-end covalent complexes between DNA and type I topoisomerases. Proc. Natl Acad. Sci. USA 93:11534–11539.
39. Pouliot J.J., Yao C.K., Robertson A.C., Nash H.A. (1999) Yeast gene for a Tyr-DNA phosphodiesterase that repairs topoisomerase I complexes. Science 286:552–555.
40. Cheng T.J., Rey G.P., Poon T., Kan C.C. (2002) Kinetic studies of human tyrosyl-DNA phosphodiesterase, an enzyme in the topoisomerase I DNA repair pathway. Eur. J. Biochem. 269:3697–3704.[ISI][Medline]
41. Connelly J.C. and Leach D.R. (2004) Repair of DNA covalently linked to protein. Mol. Cell 13:307–316.[CrossRef][ISI][Medline]
42. Davies D.R., Interthal H., Champoux J.J., Hol W.G. (2004) Explorations of peptide and oligonucleotide binding sites of tyrosyl-DNA phosphodiesterase using vanadate complexes. J. Med. Chem. 47:829–837.[CrossRef][ISI][Medline]
43. Interthal H., Pouliot J.J., Champoux J.J. (2001) The tyrosyl-DNA phosphodiesterase Tdp1 is a member of the phospholipase D superfamily. Proc. Natl Acad. Sci. USA 98:12009–12014.
44. Davies D.R., Interthal H., Champoux J.J., Hol W.G. (2002) The crystal structure of human tyrosyl-DNA phosphodiesterase, Tdp1. Structure (Camb.) 10:237–248.[Medline]
45. Davies D.R., Interthal H., Champoux J.J., Hol W.G. (2003) Crystal structure of a transition state mimic for Tdp1 assembled from vanadate, DNA, and a topoisomerase I-derived peptide. Chem. Biol. 10:139–147.[CrossRef][ISI][Medline]
46. Deng C., Brown A.J., You D., Brown J.M. (2005) Multiple endonucleases function to repair covalent topoisomerase I complexes in Saccharomyces cerevisiae. Genetics 170:591–600.
47. Pouliot J.J., Robertson A.C., Nash H.A. (2001) Pathways for repair of topoisomerase I covalent complexes in Saccharomyces cerevisiae. Genes Cells 6:677–687.[Abstract]
48. Vance J.R. and Wilson T.E. (2002) Yeast Tdp1 and Rad1-Rad10 function as redundant pathways for repairing Top1 replicative damage. Proc. Natl Acad. Sci. USA 99:13669–13674.
49. Horwitz S.B. and Horwitz M.S. (1973) Effects of camptothecin on the breakage and repair of DNA during the cell cycle. Cancer Res. 33:2834–2836.
50. D'Arpa P., Beardmore C., Liu L.F. (1990) Involvement of nucleic acid synthesis in cell killing mechanisms of topoisomerase poisons. Cancer Res. 50:6919–6924.
51. Ryan A.J., Squires S., Strutt L.H., Evans A., Johnson R.T. (1994) Different fates of camptothecin-induced replication fork-associated double-strand DNA breaks in mammalian cells. Carcinogenesis 15:823–828.
52. Poot M., Gollahon A.K., Rabinovitch P.S. (1999) Werner syndrome lymphoblastoid cells are sensitive to camptothecin-induced apoptosis in S-phase. Hum. Genet. 104:10–14.[CrossRef][ISI][Medline]
53. van Waardenburg R.C., de Jong A.L., van Delft F., van Eijndhoven M.A., Bohlander M., Bjornsti A.M., Brouwer J., Schellens J.H. (2004) Homologous recombination is a highly conserved determinant of the synergistic cytotoxicity between cisplatin and DNA topoisomerase I poisons. Mol. Cancer Ther. 3:393–402.
54. Furuta T., Takemura H., Liao Y.Z., et al. (2003) Phosphorylation of histone H2AX and activation of Mre11, Rad50, and Nbs1 in response to replication-dependent DNA double-strand breaks induced by mammalian DNA topoisomerase I cleavage complexes. J. Biol. Chem. 278:20303–20312.
55. Wu J., Yin B.M., Hapke G., Toth K., Rustum Y.M. (2002) Induction of biphasic DNA double strand breaks and activation of multiple repair protein complexes by DNA topoisomerase I drug 7-ethyl-10-hydroxy-camptothecin. Mol. Pharmacol. 61:742–748.
56. Arnaudeau C., Lundin C., Helleday T. (2001) DNA double-strand breaks associated with replication forks are predominantly repaired by homologous recombination involving an exchange mechanism in mammalian cells. J. Mol. Biol. 307:1235–1245.[CrossRef][ISI][Medline]
57. Shao R.G., Cao C.X., Zhang H., Kohn W.K., Wold S.M., Pommier Y. (1999) Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA–PK complexes. EMBO J. 18:1397–1406.[CrossRef][ISI][Medline]
58. Culmsee C., Bondada S., Mattson M.P. (2001) Hippocampal neurons of mice deficient in DNA-dependent protein kinase exhibit increased vulnerability to DNA damage, oxidative stress and excitotoxicity. Brain Res. Mol. Brain Res. 87:257–262.[Medline]
59. Godthelp B.C., Wiegant W.W., van Duijn-Goedhart A., Scharer D.O., van Buul P.P., Kanaar R., Zdzienicka M.Z. (2002) Mammalian Rad51C contributes to DNA cross-link resistance, sister chromatid cohesion and genomic stability. Nucleic Acids Res. 30:2172–2182.
60. Hinz J.M., Helleday T., Meuth M. (2003) Reduced apoptotic response to camptothecin in CHO cells deficient in XRCC3. Carcinogenesis 24:249–253.
61. Liao Z., Thibaut L., Jobson A., Pommier Y. (2006) Inhibition of human tyrosyl-DNA phosphodiesterase (Tdp1) by aminoglycoside antibiotics and ribosome inhibitors. Mol. Pharmacol. PMID: 16618796 [Epub ahead of print] (in press).
62. Interthal H., Chen J.H., Kehl-Fie E.T., Zotzmann J., Leppard B.J., Champoux J.J. (2005) SCAN1 mutant Tdp1 accumulates the enzyme—DNA intermediate and causes camptothecin hypersensitivity. EMBO J. 24:2224–2233.[CrossRef][ISI][Medline]
63. El-Khamisy S.F., Saifi M.G., Weinfeld M., Johansson F., Helleday T., Lupski R.J., Caldecott K.W. (2005) Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1. Nature 434:108–113.[CrossRef][Medline]
64. Inamdar K.V., Pouliot J.J., Zhou T., Lees-Miller P.S., Rasouli-Nia A., Povirk L.F. (2002) Conversion of phosphoglycolate to phosphate termini on 3'-overhangs of DNA double strand breaks by the human tyrosyl-DNA phosphodiesterase hTdp1. J. Biol. Chem. 277:27162–27168.
65. Interthal H., Chen J.H., Champoux J.J. (2005) Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkages. J. Biol. Chem. 280:36518–36528.
66. Liu C., Pouliot J.J., Nash H.A. (2004) The role of TDP1 from budding yeast in the repair of DNA damage. DNA Repair (Amst.) 3:593–601.[Medline]
67. Zhou T., Lee W.J., Tatavarthi H., Lupski R.J., Valerie K., Povirk L.F. (2005) Deficiency in 3'-phosphoglycolate processing in human cells with a hereditary mutation in tyrosyl-DNA phosphodiesterase (TDP1). Nucleic Acids Res. 33:289–297.
68. Parsons J.L., Dianova I.I., Dianov G.L. (2004) APE1 is the major 3'-phosphoglycolate activity in human cell extracts. Nucleic Acids Res. 32:3531–3536.
69. Pourquier P., Ueng M.L., Fertala J., Wang D., Park J.H., Essigmann M.J., Bjornsti A.M., Pommier Y. (1999) Induction of reversible complexes between eukaryotic DNA topoisomerase I and DNA-containing oxidative base damages. 7, 8-dihydro-8-oxoguanine and 5-hydroxycytosine. J. Biol. Chem. 274:8516–8523.
70. Lesher D.T., Pommier Y., Stewart L., Redinbo M.R. (2002) 8-Oxoguanine rearranges the active site of human topoisomerase I. Proc. Natl Acad. Sci. USA 99:12102–12107.
71. Chrencik J.E., Burgin B.A., Pommier Y., Stewart L., Redinbo M.R. (2003) Structural impact of the leukemia drug 1-beta-D-arabinofuranosylcytosine (Ara-C) on the covalent human topoisomerase I-DNA complex. J. Biol. Chem. 278:12461–12466.
72. Daroui P., Desai D.S., Li K.T., Liu A.A., Liu L.F. (2004) Hydrogen peroxide induces topoisomerase I-mediated DNA damage and cell death. J. Biol. Chem. 279:14587–14594.
73. Plo I., Liao Y.Z., Barcelo M.J., Kohlhagen G., Caldecott W.K., Weinfeld M., Pommier Y. (2003) Association of XRCC1 and tyrosyl DNA phosphodiesterase (Tdp1) for the repair of topoisomerase I-mediated DNA lesions. DNA Repair (Amst.) 2:1087–1100.[CrossRef][Medline]
74. Taylor R.M., Moore J.D., Whitehouse J., Johnson P., Caldecott K.W. (2000) A cell cycle-specific requirement for the XRCC1 BRCT II domain during mammalian DNA strand break repair. Mol. Cell. Biol. 20:735–740.
75. Moore D.J., Taylor M.R., Clements P., Caldecott K.W. (2000) Mutation of a BRCT domain selectively disrupts DNA single-strand break repair in noncycling Chinese hamster ovary cells. Proc. Natl Acad. Sci. USA 97:13649–13654.
76. Mol C.D., Hosfield J.D., Tainer J.A. (2000) Abasic site recognition by two apurinic/apyrimidinic endonuclease families in DNA base excision repair: the 3' ends justify the means. Mutat. Res. 460:211–229.[ISI][Medline]
77. Wilson S.H. and Kunkel T.A. (2000) Passing the baton in base excision repair. Nat. Struct. Biol. 7:176–178.[CrossRef][ISI][Medline]
78. Caldecott K.W. (2003) Protein–protein interactions during mammalian DNA single-strand break repair. Biochem. Soc. Trans. 31:247–251.[ISI][Medline]
79. Clements P.M., Breslin C., Deeks D.E., Byrd J.P., Ju L., Bieganowski P., Brenner C., Moreira C.M., Taylor M.A., Caldecott K.W. (2004) The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4. DNA Repair (Amst.) 3:1493–1502.[CrossRef][Medline]
80. Vidal A.E., Boiteux S., Hickson D.I., Radicella J.P. (2001) XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein–protein interactions. EMBO J. 20:6530–6539.[CrossRef][ISI][Medline]
81. Whitehouse C.J., Taylor M.R., Thistlethwaite A., Zhang H., Karimi-Busheri F., Lasko D.D., Weinfeld M., Caldecott K.W. (2001) XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell 104:107–117.[CrossRef][ISI][Medline]
82. Barzilai A., Rotman G., Shiloh Y. (2002) ATM deficiency and oxidative stress: a new dimension of defective response to DNA damage. DNA Repair (Amst.) 1:3–25.[CrossRef][Medline]
83. Morris E.J. and Geller H.M. (1996) Induction of neuronal apoptosis by camptothecin, an inhibitor of DNA topoisomerase-I: evidence for cell cycle-independent toxicity. J. Cell. Biol. 134:757–770.
84. Flangas A.L. and Bowman R.E. (1970) Differential metabolism of RNA in neuronal-enriched and glial-enriched fractions of rat cerebrum. J. Neurochem. 17:1237–1245.[ISI][Medline]
85. Sarkander H.I. and Uthoff C.G. (1976) Comparison of the number of RNA initiation sites in rat brain fractions enriched in neuronal or glial nuclei. FEBS Lett. 72:53–56.[Medline]
86. Sarkander H.I. and Dulce H.J. (1978) Studies on the regulation of RNA synthesis in neuronal and glial nuclei isolated from rat brain. Exp. Brain Res. 31:317–327.[ISI][Medline]
87. Yan Z. (2000) Skeletal muscle adaptation and cell cycle regulation. Exerc. Sport Sci. Rev. 28:24–26.[Medline]
88. Vierck J., O'Reilly B., Hossner K., Antonio J., Byrne K., Bucci L., Dodson M. (2000) Satellite cell regulation following myotrauma caused by resistance exercise. Cell Biol. Int. 24:263–272.[CrossRef][ISI][Medline]
89. Nouspikel T. and Hanawalt P.C. (2002) DNA repair in terminally differentiated cells. DNA Repair (Amst.) 1:59–75.[Medline]
Received on April 11, 2006;
revised on May 8, 2006;
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