期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 286, 期 39, 页码 33845-33853出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M111.274159
关键词
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资金
- National Institutes of Health (NIH) from the NIEHS [ES012512]
- NIH from the NCI [CA92584]
- NIH [CA094008]
Recent studies have implicated a poorly defined alternative pathway of nonhomologous end joining (alt-NHEJ) in the generation of large deletions and chromosomal translocations that are frequently observed in cancer cells. Here, we describe an interaction between two factors, hMre11/hRad50/Nbs1 (MRN) and DNA ligase III alpha/XRCC1, that have been linked with alt-NHEJ. Expression of DNA ligase III alpha and the association between MRN and DNA ligase III alpha/XRCC1 are altered in cell lines defective in the major NHEJ pathway. Most notably, DNA damage induced the association of these factors in DNA ligase IV-deficient cells. MRN interacts with DNA ligase III alpha/XRCC1, stimulating intermolecular ligation, and together these proteins join incompatible DNA ends in a reaction that mimics alt-NHEJ. Thus, our results provide novel mechanistic insights into the alt-NHEJ pathway that not only contributes to genome instability in cancer cells but may also be a therapeutic target.
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