期刊
EMBO REPORTS
卷 6, 期 1, 页码 83-89出版社
WILEY
DOI: 10.1038/sj.embor.7400313
关键词
DNA replication fork; flap endonuclease 1; Wemer syndrome protein
资金
- NCI NIH HHS [R01CA073763, R01 CA085344, R01CA085344] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R29CA073763, R01CA085344] Funding Source: NIH RePORTER
Restarting stalled replication forks partly depends on the break-induced recombination pathway, in which a DNA double-stranded break (DSB) is created on the stalled replication fork to initiate the downstream recombination cascades. Single-stranded DNA gaps accumulating on stalled replication forks are potential targets for endonucleases to generate DSBs. However, it is unclear how this process is executed and which nucleases are involved in eukaryotic cells. Here, we identify a novel gap endonuclease (GEN) activity of human flap endonuclease 1 (FEN-1), critical in resolving stalled replication fork. In response to replication arrest, FEN-1 interacts specifically with Werner syndrome protein for efficient fork cleavage. Replication protein A facilitates FEN-1 interaction with DNA bubble structures. Human FEN-1, but not the GEN-deficient mutant, E178A, was shown to rescue the defect in resistance to UV and camptothecin in a yeast FEN-1 null mutant.
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