期刊
DNA REPAIR
卷 7, 期 6, 页码 902-911出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.dnarep.2008.03.001
关键词
Fanconi anemia; translesion synthesis; mutagenesis; DNA repair
资金
- NHLBI NIH HHS [R01 HL052725-10, P50 HL054785, P01-HL54785, R37 HL052725, R01 HL052725, R01-HL52725, P50 HL054785-060007] Funding Source: Medline
- NIDDK NIH HHS [R01-DK43889, R01 DK043889, R01 DK043889-10] Funding Source: Medline
Fanconi anemia (FA) is a chromosome instability syndrome characterized by congenital abnormalities, cellular hypersensitivity to DNA crosslinking agents, and heightened cancer risk. Eight of the thirteen identified FA genes encode subunits of a nuclear FA core complex that monoubiquitinates FANCD2 and FANCI to maintain genomic stability in response to replication stress. The FA pathway has been implicated in the regulation of error-prone DNA damage tolerance via an undefined molecular mechanism. Here, we show that the FA core complex is required for efficient spontaneous and UVC-induced point mutagenesis, independently of FANCD2 and FANCI Consistent with the observed hypomutability of cells deficient in the FA core complex, we also demonstrate that these cells are impaired in the assembly of the error-prone translesion DNA synthesis polymerase Rev1 into nuclear foci. Consistent with a role downstream of the FA core complex and like known FA proteins, Rev1 is required to prevent DNA crosslinker-induced chromosomal aberrations in human cells. Interestingly, proliferating cell nuclear antigen (PCNA) monoubiquitination, known to contribute to Rev1 recruitment, does not require FA core complex function. Our results suggest a role for the FA core complex in regulating Rev1-dependent DNA damage tolerance independently of FANCD2, FANCI, and PCNA monoubiquitination. (c) 2008 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据