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Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, 980-8575 Sendai,1 Radioisotope Research Center, Nara Medical University, 634-8521 Nara, Japan,3 Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, United Kingdom2
Received 23 December 2002/ Returned for modification 10 February 2003/ Accepted 13 March 2003
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ABSTRACT |
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INTRODUCTION |
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In higher eukaryotes, it is known that SSB produced during base excision repair are processed by two alternative repair pathways, a DNA polymerase ß (Polß)-dependent pathway and a proliferating cell nuclear antigen (PCNA)-dependent pathway. Selection of these pathways is considered to be damage and/or dose dependent (12). Poly(ADP-ribosyl)ation, a posttranslational modification of proteins catalyzed by DNA-dependent poly(ADP-ribose) polymerase (PARP), occurs very rapidly in response to SSB. PARP-1 has been proposed to play a key role in SSB repair by its rapid binding to SSB and subsequent activation (3). PARP-2 is also activated by SSB and participates in the repair of SSB (2, 31). XRCC1 is another protein that plays a central role in the repair of SSB. In biochemical studies, XRCC1 was shown to interact with activated PARP-1 (8, 22, 31) and PARP-2 (31), OL ß (6, 21), DNA ligase III
(4, 5), AP endonuclease (39), and polynucleotide kinase (42). By these interactions, XRCC1 is thought to play a key role in coordinating the DNA OL ß-dependent base excision repair pathway and SSB repair (7).
The repair mechanisms for SSB and base excision repair proposed so far have mainly been examined in in vitro cell-free systems reconstituted with purified proteins and/or cell extracts. Since the actions of the DNA repair proteins are performed at the relevant stage (e.g., on complex chromatin substrates) in time-dependent processes, any in vitro assay tends to overlook crucial biological processes and effects. To elucidate the in vivo repair process of SSB, we previously established a nucleotide excision repair-deficient xeroderma pigmentosum group A (XPA) cell line expressing Neurospora crassa UV damage endonuclease (UVDE) (27). UVDE introduces an SSB with a 3'-OH immediately 5' to UV-induced cyclobutane pyrimidine dimers, 6-4 photoproducts, and Dewar photoproducts (13, 16, 33, 44, 45). We showed that in these cells (XPA-UVDE cells), SSB are produced immediately after UV irradiation by the action of UVDE on various UV-induced DNA lesions, and SSB together with UV-induced lesions are then efficiently repaired (27). A PARP inhibitor, 3-aminobenzamide (3-AB), increases the UV sensitivity of the cells, and XRCC1-deficient Chinese hamster cells harboring UVDE are highly UV sensitive, suggesting the involvement of PARP and XRCC1 in the process of repair of UVDE-induced SSB. We found that the repair synthesis of the SSB is a long-patch repair, with a mean patch size of seven nucleotides (27), suggesting that PARP, XRCC1, and aphidicolin-sensitive DNA polymerase(s) participate in this SSB repair. Since the cells do not possess nucleotide excision repair, UV-induced lesions are processed exclusively by UVDE and subsequent SSB repair. Thus, the XPA-UVDE cell offers a unique experimental system with which to create SSB by UV irradiation.
In order to analyze cellular responses to SSB and dynamic correlations between DNA repair proteins, we made use of a recently developed technique to inflict UV damage in restricted small regions of the nucleus (local UV irradiation) for XPA-UVDE cells. By using antibodies and fluorescence microscopy, the temporal and spatial behavior of the principal proteins involved in the repair of SSB were visualized within the nucleus for the first time.
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MATERIALS AND METHODS |
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DNA transfection. DNA constructs were made according to standard procedures (30). Briefly, the cDNA of full-length XRCC1 as well as various fragments of XRCC1 were amplified by PCR with 5' and 3' primers containing SalI and NotI sites, respectively. The amplified DNA fragments were subcloned into the XhoI and NotI sites of pCY4B-Flag, a modified pCY4B plasmid (26) containing a chicken ß-actin promoter which drives the expression of an in-frame N-terminal Flag peptide tag. Two additional pCY4B-Flag constructs of XRCC1 mutants having amino acid replacement mutations in the BRCT1 domain were constructed by PCR with plasmids pcD2EXH W385D and pcD2EXH LI360/361 DD (36) as templates and the same primers used for the full-length XRCC1. The DNA constructs were verified by sequencing. These plasmids were introduced into XPA-UVDE cells with Fugene 6 (Roche) according to the manufacturer's protocol.
Local UV irradiation. Local UV irradiation was performed essentially as described previously (17). Cell monolayers in 35-mm glass-bottomed culture dishes (poly-D-lysine coated; MatTek, Ashland, Oreg.) were covered with a polycarbonate isopore membrane filter with pores of 3 µm in diameter (Millipore) and UV irradiated with a germicidal lamp (GL-10; Toshiba; predominantly 254-nm UV) at a dose rate of 1.82 J/m2/s. The polycarbonate blocks the 254-nm UV light, and cells are exposed only through the pores of the filter. A filter with a larger pore size results in larger spots of poly(ADP-ribose) synthesis, indicating that SSB are produced only at the UV-exposed areas (see Results).
Immunofluorescence microscopy. For immunolabeling, XPA-UVDE or XPA-Vector cells were grown for 2 days in glass-bottomed culture dishes, and almost confluent cultures were UV irradiated. To examine the effect of inhibitors of PARP, cells were incubated for 1 h in medium supplemented with 1,5-dihydroxyisoquinoline (DIQ; 100 µM; Sigma) or 3-aminobenzamide (3-AB; 4 mM; Sigma) before irradiation and washed twice with Hanks' solution (Nissui) with DIQ or 3-AB. Then the cells were irradiated with UV at 20 J/m2 as described above. After UV irradiation, cells were incubated in medium with DIQ or 3-AB at 37°C for various periods of time and then fixed with methanol-acetone (1:1) for 10 min at -20°C. The fixed cells were dried, subsequently rinsed once with TNT buffer (0.1 M Tris-HCl, 0.15 M NaCl, 0.05% Tween 20, pH 7.5), and then incubated in TNB buffer (TNT buffer containing blocking reagent [NEN]) at 30°C for 30 min. Cells were then incubated with anti-XRCC1 antibody (ab144; Abcam) at a 1:150 dilution in TNB buffer at 30°C for 1 h.
For observation of the Flag-tagged proteins, XPA-UVDE cells grown in dishes were transfected with the plasmids mentioned above. At 24 h following transfection, cells were treated and UV irradiated as described above. For labeling the Flag-tagged proteins, rabbit anti-Flag (5 µg/ml; Sigma) was used. Cells treated with antibodies against XRCC1 and Flag were then washed three times with TNT buffer and incubated with Alexa Fluor 594 goat anti-rabbit immunoglobulin G conjugate (Molecular Probes) at a 1:400 dilution in TNB buffer for 1 h. After washing with TNT buffer, cells were then incubated with anti-poly(ADP-ribose) (1:200 dilution; Trevigen) or antinucleolin/C23 (1:25 dilution; MS-3; Santa Cruz) or anti-PARP-1 (1:25 dilution; F-2; Santa Cruz) in TNB buffer for 1 h. After washing treatments, cells were incubated with Alexa Fluor 488 goat anti-mouse immunoglobulin G conjugate (Molecular Probes) at a 1:400 dilution in TNB buffer for 1 h. Cell samples were then mounted in drops of PermaFluor (Immunon), and coverslips were added. Confocal imaging was performed with an Olympus FV-500 confocal laser system connected to an Olympus microscope (IX81) with a 60x oil immersion objective lens (PlanApo).
For double staining of PCNA and CAF-1 p150, cells were further treated before fixation with ice-cold detergent solution (0.5% Triton X-100, 0.2 mg of EDTA per ml, and 1% bovine serum albumin in phosphate-buffered saline) for 15 min and washed with phosphate-buffered saline. Then cells were fixed with methanol-acetone and treated as described above. Cells were labeled successively with anti-PCNA (1:25 dilution; FL-261; Santa Cruz), Alexa Fluor 594 goat anti-rabbit immunoglobulin G conjugate, anti-CAF-1 p150 monoclonal antibody (1:250 dilution; SS1; a kind gift from B. Stillman, Cold Spring Harbor Laboratory), and Alexa Fluor 488 goat anti-mouse immunoglobulin G conjugate. Nuclear DNA was counterstained with 4',6'-diamidino-2-phenylindole (DAPI; Wako; 0.5 µg/ml). Cell samples were mounted, and coverslips were added as described above. Fluorescence microscopic images were obtained with a Leica model DMLB30. Images were captured by charge-coupled device camera (DC250; Leica) and colored with Qfluoro software (Leica).
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RESULTS |
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After local UV irradiation, cells were fixed and then immunolabeled with antibodies against PAR. Before irradiation, no evident PAR was observed (Fig. 1a, upper panel). Two minutes after irradiation, PAR synthesis was observed in restricted spots in the nucleus with diameters comparable to the pore size (Fig. 1b, upper panel). Ten minutes after irradiation, the sizable amount of PAR in the spots had faded away (Fig. 1c, upper panel), and 30 min after irradiation, these spots were almost indiscernible (Fig. 1d, upper panel). In irradiated XPA cells harboring empty vector plasmid (XPA-Vector cells), no PAR synthesis was observed (Fig. 1f, upper panel).
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Poly(ADP ribosyl)ation-dependent accumulation of XRCC1 in SSB. Before irradiation, XRCC1 was found in many small dots of various sizes in addition to a faint background in the nucleus (Fig. 1a, middle panel, and see the next section). Two minutes after irradiation, XRCC1 had already accumulated at the irradiated spots (Fig. 1b, middle panel), which completely overlapped the sites of synthesis of PAR (Fig. 1b, bottom panel), while the amount of XRCC1 in unirradiated nuclear regions had drastically decreased (Fig. 1b, middle panel). This shows that, upon UV irradiation, XRCC1 translocated from the unirradiated nuclear region to the irradiated spots. In XPA-Vector cells, the recruitment of XRCC1 was not observed after irradiation (Fig. 1f, middle panel). In the presence of DIQ (Fig. 1e, middle panel) or 3-AB (data not shown), no translocation of XRCC1 to the irradiated spots was observed in XPA-UVDE cells. These results indicate that the synthesis of PAR at the sites of SSB is a prerequisite for XRCC1 accumulation at SSB and also that the translocation of XRCC1 from throughout the nucleus to SSB is triggered by the synthesis of PAR. In contrast to PAR, the intensities of the spots of XRCC1 were not drastically changed 10 and 30 min after irradiation (Fig. 1c and 1d, middle panels, respectively).
Distribution of XRCC1 and PARP-1 in nucleoli and nucleoplasm. As shown in the previous section, XRCC1 was distributed throughout the nucleus of unirradiated cells. We found that a part of XRCC1 was located in relatively large foci (Fig. 2Aa, top). These foci were identified as the nucleoli by costaining the cells with antibody to the nucleolar protein nucleolin (14) (Fig. 2Aa, middle and bottom panels). In HeLa cells harboring larger nucleoli, the presence of XRCC1 in the nucleoli was much more evident (Fig. 2Ad). Two minutes after irradiation, most of the XRCC1 present in the nucleoli as well as in the nucleoplasm had translocated to the irradiated sites (Fig. 2Ab). In XPA-Vector cells, no discernible translocation of XRCC1 was observed after irradiation (Fig. 2Ac).
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In situ determination of domain in XRCC1 responsible for recruitment to SSB. In order to identify which part of XRCC1 is necessary for the recruitment to SSB sites in situ, we used deletions and site-specific mutagenesis. A series of expression constructs harboring various XRCC1 fragments and two BRCT1 domain mutants with amino acid replacement mutations (W385D and LI360/361DD) were tagged with the Flag epitope at the NH2 terminus and transiently expressed in XPA-UVDE cells. They were then assayed for their ability to be recruited to the PAR-synthesized spots (Fig. 3). As shown in Fig. 3Aa, the full-length Flag-XRCC1 accumulated in nuclear foci in transfected cells, as described previously (35). However, Flag-XRCC1 was not present in nucleoli, nor was XRCC1 which had been tagged with green fluorescent protein (GFP) at the carboxyl terminus located in nucleoli (data not shown), suggesting that the nucleolar distribution of XRCC1 may be very sensitive to its modification.
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Transfected XRCC1 fragment containing the BRCT2 domain (538 to 633) without the nuclear localization signal (22) was diffusely distributed throughout the cell, including the nucleus, and was not recruited to the irradiated spots after irradiation (data not shown). Significantly, two BRCT1 domain mutants corresponding to the mutants of the BRCT2 domain shown previously to disrupt its folding (46) or activity (24, 34) were not recruited to irradiated spots (Fig. 3B). These results indicate that the BRCT1 domain, the site for interacting with poly(ADP-ribosyl)ated PARP-1 (22) and PARP-2 (31), plays a crucial role in the recruitment of XRCC1 to SSB.
In situ visualization of assembly of PCNA and CAF-1 at SSB. PCNA is known to take a detergent-resistant chromatin-bound form during S phase and also after DNA damage induced by UV (18), hydrogen peroxide, or alkylating drugs (12). Chromatin assembly factor 1 (CAF-1) is a histone chaperone that has a role in chromatin assembly during DNA replication and nucleotide excision repair (18). CAF-1 p150 interacts directly with PCNA (23, 32). Involvement of PCNA and the largest subunit (p150) of CAF-1 in the repair of SSB was analyzed in our cell system. Cells were irradiated, permeabilized with Triton X-100, fixed, and then analyzed by immunofluorescence microscopy.
In unirradiated control cells, about 34% of nuclei were found to be in S phase, each having detergent-resistant PCNA and CAF-1 p150 throughout the nucleus (red-stained PCNA and green-stained CAF-1 p150 in Fig. 4Aa, first and second upper panels). Following local irradiation of the cells, detergent-insoluble PCNA and CAF-1 p150 were detected at irradiated spots in cells not in S phase (Fig. 4Ab). The spots overlapped each other (Fig. 4Ab). Cells synchronized in G1 phase by treatment with mimosine were also examined. In these cells, S-phase nuclei disappeared almost completely (data not shown). After irradiation, detergent-resistant spots were observed in every nucleus (Fig. 4Be), while these spots were not observed in either asynchronous or G1-phase cells after irradiation in XPA-Vector cells (Fig. 4Ad and Bf). Thus, the observed detergent-resistant PCNA and CAF-1 p150 do not reflect DNA replication in S-phase cells but do reflect SSB-dependent accumulation and suggest that a PCNA-dependent process is accompanied by chromatin-assembly mediated by CAF-1.
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DISCUSSION |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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First of all, by production of SSB at the UV-irradiated areas in the nucleus, we demonstrated that the transient synthesis of PAR occurs at the restricted area of SSB in the actual context of the nucleus (Fig. 1). This may be the first in situ visual demonstration of the widely accepted model for PARP activation based on in vitro results. Second, we showed that before UV irradiation, XRCC1 protein was present throughout the nucleus, including nucleoli (Fig. 2). Park et al. reported that XRCC1 was not observed in the nucleolus (28). This discrepancy may be due to the difference in the fixation procedures and/or antibodies used in the experiments. The binding of XRCC1 to the structural component of the nucleolus may be weak, as tagged constructs of XRCC1 were not observed in the nucleolus. XRCC1 has been proposed to serve as the molecular scaffold or docking platform for other repair proteins (7, 21). Nucleoli may simply be a storage place for XRCC1. However, it is tempting to consider that this nucleolar localization may be responsible for some other unidentified functions of XRCC1 in transcription or recombination, as proposed previously (37, 39).
Depending on the presence of PAR at SSB, XRCC1 is recruited very rapidly and efficiently from throughout the nucleus distant from the sites of SSB (Fig. 1 and 2). In accordance with these results, after treatment of HeLa cells with H2O2 the distinct nucleolar XRCC1 disappeared, suggesting that H2O2-induced SSB also recruit XRCC1 (data not shown). Our results suggest that XRCC1-mediated repair is considerably impaired in PARP-deficient cells compared with wild-type cells. In agreement with this, the high sensitivity of PARP-1 knockout mice and the derived mouse embryonic fibroblasts to alkylating agents and gamma irradiation (38) and prolonged delays in SSB repair in PARP-1- and PARP-2-deficient cells following treatment with alkylating agents (31, 38) have been reported.
The region near the N terminus of XRCC1 binds to OL ß (21), and the BRCT2 domain at the C terminus of XRCC1 binds to DNA ligase III (25). By deletion analysis along with site-specific mutagenesis, we demonstrated that the BRCT1 domain of XRCC1 protein, the interaction site with poly(ADP-ribosyl)ated PARP-1 (22) and PARP-2 (31), is responsible for its recruitment to SSB (Fig. 3). Thus, the ability of XRCC1 to bind SSB, OL ß, and DNA ligase III was not necessarily required for its recruitment to SSB (Fig. 3). The C-terminal portion of the BRCT1 domain of XRCC1 (379 to 400; PAR-binding site) has recently been reported to interact noncovalently with PAR (29). Our present results showed that XRCC1 fragments 1 to 378 and 242 to 378 devoid of the PAR-binding site were not recruited after irradiation (Fig. 3). Thus, the site for interacting with PAR may play an essential role in the recruitment of XRCC1 to SSB.
Two XRCC1 mutants (XRCC1W385D and LI360/361DD) could not repair SSB in G1 or S/G2 phase (36), while the XRCC1 W385D mutant still bound to OL ß and DNA ligase III in vitro (36). We showed that these mutant XRCC1 forms were not recruited to SSB (Fig. 3). These results, together with the deletion data, strongly suggest that the ability of XRCC1 to bind to activated PARP plays an indispensable role in both G1- and S/G2-specific repair. In striking contrast to XRCC1, no discernible translocation of PARP-1 to the SSB was observed after local irradiation (Fig. 2B). This may be due to the amount of PARP-1, which is normally present in considerable molar excess (threefold) compared with XRCC1 (37), or may be due to the accumulation of many XRCC1 molecules in one poly(ADP-ribosyl)ated PARP at SSB.
We showed that a PCNA-dependent process is involved in the repair of the SSB introduced by UVDE (Fig. 4). This is consistent with our previous result showing that after whole-cell UV irradiation with 20 J/m2, repair synthesis was decreased to about 30% by aphidicoline, suggesting polymerase 
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-dependent long-patch repair for UVDE-induced SSB (27). Our present results suggest that this pathway is accompanied by chromatin assembly mediated by CAF-1 (Fig. 4). This is the first demonstration that the chromatin assembly mediated by CAF-1 is involved in the process of SSB repair in vivo. The recruitment of both PCNA and CAF-1 p150 was reduced in the absence of PAR at the sites of SSB. In contrast to XRCC1, the assembly of PCNA with SSB does not fully depend on the synthesis of PAR (Fig. 4). These results are in harmony with a model to explain the function at the molecular level: by PARP activation at SSB, the relaxation or opening-up of chromatin superstructure by covalent or noncovalent modification of histones by PAR occurs, allowing access for the DNA repair machinery to the SSB (1, 10). In the presence of PARP inhibitors, PARP-1 and probably histones would remain bound to SSB and may partially block the access of the PCNA-loading machinery and CAF-1, thereby reducing the assembly of these proteins at SSB. Our results indicate the involvement of PAR synthesis in the PCNA-dependent repair of SSB.
Sequential assembly of repair proteins at the sites of DNA damage has been considered to enable various DNA repair systems to work quite effectively. So far, in vitro studies with purified proteins and cell extracts along with structural studies have clarified many features and provided various models for base excision repair and SSB repair processes (7, 42, 43). Our in situ results show that SSB repair is a sequential process in which the order of protein assembly is regulated by PAR. Although many questions concerning the processes by which SSB are repaired remain open, our experimental system provides a powerful tool for understanding the spatial and temporal aspects of the cellular responses to SSB in situ, as exemplified here.
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ACKNOWLEDGMENTS |
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This work was supported by Grants-in-Aid for Scientific Research (no. 12143201 and no. 13480162) from the Ministry of Education, Science, Sports and Culture of Japan and by the Mitsubishi Foundation to A.Y.
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FOOTNOTES |
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REFERENCES |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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2. Ame, J. C., V. Rolli, V. Schreiber, C. Niedergang, F. Apiou, P. Decker, S. Muller, T. Hoger, J. Menissier-de Murcia, and G. de Murcia. 1999. PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase. J. Biol. Chem. 274:17860-17868.
3. Burkle, A. 2001. Physiology and pathophysiology of poly(ADP-ribosyl)ation. Bioessays 23:795-806.[CrossRef][Medline]
4. Caldecott, K. W., C. K. McKeown, J. D. Tucker, S. Ljungquist, and L. H. Thompson. 1994. An interaction between the mammalian DNA repair protein XRCC1 and DNA ligase III. Mol. Cell. Biol. 14:68-76.
5. Caldecott, K. W., J. D. Tucker, L. H. Stanker, and L. H. Thompson. 1995. Characterization of the XRCC1-DNA ligase III complex in vitro and its absence from mutant hamster cells. Nucleic Acids Res. 23:4836-4843.
6. Caldecott, K. W., S. Aoufouchi, P. Johnson, and S. Shall. 1996. XRCC1 polypeptide interacts with DNA polymerase beta and possibly poly (ADP-ribose) polymerase, and DNA ligase III is a novel molecular 'nick-sensor' in vitro. Nucleic Acids Res. 24:4387-4394.
7. Caldecott, K. W. 2001. Mammalian DNA single-strand break repair: an X-ra(y)ted affair. Bioessays 23:447-455.[CrossRef][Medline]
8. Dantzer, F., G. de la Rubia, J. Menissier-de Murcia, Z. Hostomsky, G. de Murcia, and V. Schreibr. 2000. Base excision repair is impaired in mammalian cells lacking poly(ADP-ribose) polymerase-1. Biochemistry 39:7559-7569.[CrossRef][Medline]
9. Davidovic, L., M. Vodenicharov, E. B. Affar, and G. G. Poirier. 2001. Importance of poly(ADP-ribose) glycohydrolase in the control of poly(ADP-ribose) metabolism. Exp. Cell Res. 268:7-13.[CrossRef][Medline]
10. de Murcia, G., A. Huletsky, and G. G. Poirier. 1988. Modulation of chromatin structure by poly(ADP-ribosyl)ation. Biochem. Cell Biol. 66:626-635.[Medline]
11. Desnoyers, S., S. H. Kaufmann, and G. G. Poirier. 1996. Alteration of the nucleolar localization of poly(ADP-ribose) polymerase upon treatment with transcription inhibitors. Exp. Cell Res. 227:146-153.[CrossRef][Medline]
12. Dogliotti, E., P. Fortini, B. Pascucci, and E. Parlanti. 2001. The mechanism of switching among multiple base excision repair pathways. Prog. Nucleic Acid Res. Mol. Biol. 68:3-27.
13. Freyer, G. A., S. Davey, J. V. Ferrer, A. M. Martin, D., Beachand, and P. W. Doetsch. 1995. An alternative eukaryotic DNA excision repair pathway. Mol. Cell. Biol. 15:4572-4577.[Abstract]
14. Ginisty, H., H. Sicard, B. Rogerand, and P. Bouvet. 1999. Structure and functions of nucleolin. J. Cell Sci. 112:761-772.[Abstract]
15. Imoto, K., N. Kobayashi, S. Katsumi, Y. Nishiwaki, T. A. Iwamoto, A. Yamamoto, Y. Yamashina, T. Shirai, S. Miyagawa, Y. Dohi, S. Sugiura, and T. Mori. 2002. The total amount of DNA damage determines ultraviolet-radiation-induced cytotoxicity after uniformor localized irradiation of human cells. J. Investig. Dermatol. 119:1177-1182.[CrossRef][Medline]
16. Kanno, S., S. Iwai, M. Takao, and A. Yasui. 1999. Repair of apurinic/apyrimidinic sites by UV damage endonuclease; a repair protein for UV and oxidative damage. Nucleic Acids Res. 27:3096-3103.
17. Katsumi, S., N. Kobayashi, K. Imoto, A. Nakagawa, Y. Yamashina, T. Muramatsu, T. Shirai, S. Miyagawa, S. Sugiura, F. Hanaoka, T. Matsunaga, O. Nikaido, and T. Mori. 2001. In situ visualization of ultraviolet-light-induced DNA damage repair in locally irradiated human fibroblasts. J. Investig. Dermatol. 117:1156-1161.[CrossRef][Medline]
18. Kaufman, P. D., and G. Almouzni. 2000. DNA replication, nucleotide excision repair, and nucleosome assembly, p. 24-48. In S. C. R. Elgin and J. L.Workman (ed.) Chromatin structure and gene expression, 2nd ed. Oxford University Press, New York, N.Y.
19. Kowalczykowski, S. C. 2000. Initiation of genetic recombination and recombination-dependent replication. Trends Biochem. Sci. 25:156-165.[CrossRef][Medline]
20. Krude, T. 1999. Mimosine arrests proliferating human cells before onset of DNA replication in a dose-dependent manner. Exp. Cell Res. 247:148-159.[CrossRef][Medline]
21. Kubota, Y., R. A. Nash, A. Klungland, P. Schar, D. E. Barnes, and T. Lindahl. 1996. Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein. EMBO J. 15:6662-6670.[Medline]
22. Masson, M., C. Niedergang, V. Schreiber, S. Muller, J. Menissier-de Murciaand, and G. de Murcia. 1998. XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage. Mol. Cell. Biol. 18:3563-3571.
23. Moggs, J. G., P. Grandi, J. P. Quivy, Z. O. Jonsson, U. Hubscher, P. B. Becker, and G. Almouzni. 2000. A CAF-1-PCNA-mediated chromatin assembly pathway triggered by sensing DNA damage. Mol. Cell. Biol. 20:1206-1218.
24. Moore, D. J., R. M. Taylor, P. Clements, and K. W. Caldecott. 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.
25. Nash, R. A., K. W. Caldecott, D. E. Barnes, and T. Lindahl. 1997. XRCC1 protein interacts with one of two distinct forms of DNA ligase III. Biochemistry 36:5207-5211.[CrossRef][Medline]
26. Niwa, H., K. Yamamura, and J. Miyazaki. 1991. Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 108:193-200.[CrossRef][Medline]
27. Okano, S., S. Kanno, S. Nakajima, and A. Yasui. 2000. Cellular responses and repair of single-strand breaks introduced by UV damage endonuclease in mammalian cells. J. Biol. Chem. 275:32635-32641.
28. Park, S. Y., W. Lam, and Y. C. Cheng. 2002. X-ray repair cross-complementing gene I protein plays an important role in camptothecin resistance. Cancer Res. 62:459-465.
29. Pleschke, J. M., H. E. Kleczkowska, M. Strohmand, and F. R. Althaus. 2000. Poly(ADP-ribose) binds to specific domains in DNA damage checkpoint proteins. J. Biol. Chem. 275: 40974-40980.
30. Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular cloning: a laboratory manual, 2nd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
31. Schreiber, V., J. C. Ame, P. Dolle, I. Schultz, B. Rinaldi, V. Fraulob, J. Menissier-de Murcia, and G. de Murcia. 2002. Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1. J. Biol. Chem. 277:23028-23036.
32. Shibahara K.-I., and B. Stillman. 1999. Replication-dependent marking of DNA by PCNA facilitates CAF-1-coupled inheritance of chromatin. Cell 96:575-585.[CrossRef][Medline]
33. Takao, M., R. Yonemasu, K. Yamamoto, and A. Yasui. 1996. Characterization of a UV endonuclease gene from the fission yeast Schizosaccharomyces pombe and its bacterial homolog. Nucleic Acids Res. 24:1267-1271.
34. Taylor, R. M., B. Wickstead, S. Cronin, and K. W. Caldecott. 1998. Role of a BRCT domain in the interaction of DNA ligase III-alpha with the DNA repair protein XRCC1. Curr. Biol. 16:877-880.
35. Taylor, R. M., D. J. Moore, J. Whitehouse, P. Johnson, and K. W. Caldecott. 2000. A cell cycle-specific requirement for the XRCC1 BRCT II domain during mammalian DNA strand break repair. Mol. Cell. Biol. 20:735-740.
36. Taylor, R. M., A. Thistlethwaite, and K. W. Caldecott. 2002. Central role for the XRCC1 BRCT I domain in mammalian DNA single-strand break repair. Mol. Cell. Biol. 22:2556-2563.
37. Thompson, L. H., and M. G. West. 2000. XRCC1 keeps DNA from getting stranded. Mutat. Res. 459:1-18.[Medline]
38. Trucco, C., F. J. Oliver, G. de Murcia, and J. Menissier-de Murcia. 1998. DNA repair defect in poly(ADP-ribose) polymerase-deficient cell lines. Nucleic Acids Res. 26:2644-2649.
39. Vidal, A. E., S. Boiteux, I. D. Hickson, and J. P. Radicella. 2001. XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions. EMBO J. 20:6530-6539.[CrossRef][Medline]
40. Virag, L., and C. Szabo. 2002. The therapeutic potential of poly(ADP-Ribose) polymerase inhibitors. Pharmacol. Rev. 54:375-429.
41. Volker, M., M. J. Mone, P. Karmakar, A. van Hoffen, W. Schul, W. Vermeulen, J. H. Hoeijmakers, R. van Driel, A. A. van Zeeland, and L. H. Mullenders. 2001. Sequential assembly of the nucleotide excision repair factors in vivo. Mol. Cell 8:213-224.[CrossRef][Medline]
42. Whitehouse, C. J., R. M. Taylor, A. Thistlethwaite, H. Zhang, F. Karimi-Busheri, D. D. Lasko, M. Weinfeld, and K. W. Caldecott. 2001. XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell 104:107-117.[CrossRef][Medline]
43. Wilson, S. H., and T. A. Kunkel. 2000. Passing the baton in base excision repair. Nat. Struct. Biol. 7:176-178.[CrossRef][Medline]
44. Yajima, H., M. Takao, S. Yasuhira, J. H. Zhao, C. Ishii, H. Inoue, and A. Yasui. 1995. A eukaryotic gene encoding an endonuclease that specifically repairs DNA damaged by ultraviolet light. EMBO J. 14:2393-2399.[Medline]
45. Yasui, A., and S. J. McCready. 1998. Alternative repair pathways for UV-induced DNA damage. Bioessays 20:291-297.[CrossRef][Medline]
46. Zhang, X., S. Morera, P. A. Bates, P. C. Whitehead, A. I. Coffer, K. Hainbucher, R. A. Nash, M. J. Sternberg, T. Lindahl, and P. S. Freemont. 1998. Structure of an XRCC1 BRCT domain: a new protein-protein interaction module. EMBO J. 17:6404-6411.[CrossRef][Medline]
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