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Novel function of the flap endonuclease 1 complex in processing stalled DNA replication forks
Author(s) -
Zheng Li,
Zhou Mian,
Chai Qing,
Parrish Jay,
Xue Ding,
Patrick Steve M,
Turchi John J,
Yan Steven M,
Chen David,
Shen Binghui
Publication year - 2005
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400313
Subject(s) - biology , control of chromosome duplication , dna replication , microbiology and biotechnology , endonuclease , replication factor c , ter protein , origin recognition complex , eukaryotic dna replication , genetics , replication protein a , pre replication complex , dna , dna binding protein , gene , transcription factor
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.