期刊
DNA REPAIR
卷 10, 期 11, 页码 1145-1153出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.dnarep.2011.08.012
关键词
Mismatch repair; Poly[ADP-ribose] polymerase; MutS alpha; Exonuclease
资金
- National Institutes of Health [GM45190]
End-directed mismatch-provoked excision has been reconstituted in several purified systems. While 3'-directed excision displays a mismatch dependence similar to that observed in nuclear extracts (approximate to 20-fold), the mismatch dependence of 5'-directed excision is only 3-4-fold, significantly less than that in extracts (8-10-fold). Utilizing a fractionation-based approach, we have isolated a single polypeptide that enhances mismatch dependence of reconstituted 5'-directed excision and have shown it to be identical to poly[ADP-ribose] polymerase 1 (PARP-1). Titration of reconstituted excision reactions or PARP-1-depleted HeLa nuclear extract with purified PARP-1 showed that the protein specifically enhances mismatch dependence of 5'-directed excision. Analysis of a set of PARP-1 mutants revealed that the DNA binding domain and BRCT fold contribute to the regulation of excision specificity. Involvement of the catalytic domain is restricted to its ability to poly(ADP-ribosyl)ate PARP-1 in the presence of NAD(+), likely through interference with DNA binding. Analysis of protein-protein interactions demonstrated that PARP-1 interacts with mismatch repair proteins MutS alpha, exonuclease 1, replication protein A (RPA), and as previously shown by others, replication factor C (RFC) and proliferating cell nuclear antigen (PCNA) as well. The BRCT fold plays an important role in the interaction of PARP-1 with the former three proteins. (C) 2011 Elsevier B.V. All rights reserved.
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