Novel function of the flap endonuclease 1 complex in processing stalled DNA replication forks

Li Zheng, Mian Zhou, Qing Chai, Jay Parrish, Ding Xue, Steve M. Patrick, John J. Turchi, Steven M. Yannone, David Chen, Binghui Shen

Research output: Contribution to journalArticle

98 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)83-89
Number of pages7
JournalEMBO Reports
Volume6
Issue number1
DOIs
StatePublished - Dec 8 2005

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Keywords

  • DNA replication fork
  • Flap endonuclease 1
  • Werner syndrome protein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Zheng, L., Zhou, M., Chai, Q., Parrish, J., Xue, D., Patrick, S. M., Turchi, J. J., Yannone, S. M., Chen, D., & Shen, B. (2005). Novel function of the flap endonuclease 1 complex in processing stalled DNA replication forks. EMBO Reports, 6(1), 83-89. https://doi.org/10.1038/sj.embor.7400313