Fen-1 facilitates homologous recombination by removing divergent sequences at DNA break ends
Fen-1 facilitates homologous recombination by removing divergent sequences at DNA break ends
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DOI：
10.1128/mcb.25.16.6948-6955.2005
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发表时间：
2005-08-01
影响因子：
5.3
通讯作者：
Takeda, S
中科院分区：
文献类型：
--
作者：
Kikuchi, K;Taniguchi, Y;Takeda, S
Homologous recombination (HR) requires nuclease activities at multiple steps, but the contribution of individual nucleases to the processing of double-strand DNA ends at different stages of HR has not been clearly defined. We used chicken DT40 cells to investigate the role of flap endonuclease 1 (Fen-1) in HR. FEN-1-deficient cells exhibited a significant decrease in the efficiency of immunoglobulin gene conversion while being proficient in recombination between sister chromatids, suggesting that Fen-1 may play a role in HR between sequences of considerable divergence. To clarify whether sequence divergence at DNA ends is truly the reason for the observed HR defect in FEN-1(-/-) cells we inserted a unique I-SceI restriction site in the genome and tested various donor and recipient HR substrates. We found that the efficiency of HR-mediated DNA repair was indeed greatly diminished when divergent sequences were present at the DNA break site. We conclude that Fen-1 eliminates heterologous sequences at DNA damage site and facilitates DNA repair by HR.
