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 Turchi, Steven M. Yannone, David Chen, Binghui Shen

Research output: Contribution to journalArticle

97 Citations (Scopus)

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 - 2005
Externally publishedYes

Fingerprint

Flap Endonucleases
DNA Replication
Endonucleases
DNA
Processing
Genetic Recombination
Replication Protein A
Werner Syndrome
Camptothecin
Double-Stranded DNA Breaks
Single-Stranded DNA
Eukaryotic Cells
Human Activities
Yeast
Yeasts
Defects
Proteins

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Zheng, L., Zhou, M., Chai, Q., Parrish, J., Xue, D., Patrick, S. M., ... 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

Novel function of the flap endonuclease 1 complex in processing stalled DNA replication forks. / Zheng, Li; Zhou, Mian; Chai, Qing; Parrish, Jay; Xue, Ding; Patrick, Steve M.; Turchi, John; Yannone, Steven M.; Chen, David; Shen, Binghui.

In: EMBO Reports, Vol. 6, No. 1, 2005, p. 83-89.

Research output: Contribution to journalArticle

Zheng, L, Zhou, M, Chai, Q, Parrish, J, Xue, D, Patrick, SM, Turchi, J, Yannone, SM, Chen, D & Shen, B 2005, 'Novel function of the flap endonuclease 1 complex in processing stalled DNA replication forks', EMBO Reports, vol. 6, no. 1, pp. 83-89. https://doi.org/10.1038/sj.embor.7400313
Zheng, Li ; Zhou, Mian ; Chai, Qing ; Parrish, Jay ; Xue, Ding ; Patrick, Steve M. ; Turchi, John ; Yannone, Steven M. ; Chen, David ; Shen, Binghui. / Novel function of the flap endonuclease 1 complex in processing stalled DNA replication forks. In: EMBO Reports. 2005 ; Vol. 6, No. 1. pp. 83-89.
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