A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses

Shin Ichiro Kanno, Hiroyuki Kuzuoka, Shigeru Sasao, Zehui Hong, Li Lan, Satoshi Nakajima, Akira Yasui

Research output: Contribution to journalArticlepeer-review

105 Citations (Scopus)

Abstract

DNA damage causes genome instability and cell death, but many of the cellular responses to DNA damage still remain elusive. We here report a human protein, PALF (PNK and APTX-like FHA protein), with an FHA (forkhead-associated) domain and novel zinc-finger-like CYR (cysteine-tyrosine-arginine) motifs that are involved in responses to DNA damage. We found that the CYR motif is widely distributed among DNA repair proteins of higher eukaryotes, and that PALF, as well as a Drosophila protein with tandem CYR motifs, has endo- and exonuclease activities against abasic site and other types of base damage. PALF accumulates rapidly at single-strand breaks in a poly(ADP-ribose) polymerase 1 (PARP1)-dependent manner in human cells. Indeed, PALF interacts directly with PARP1 and is required for its activation and for cellular resistance to methyl-methane sulfonate. PALF also interacts directly with KU86, LIGASEIV and phosphorylated XRCC4 proteins and possesses endo/exonuclease activity at protruding DNA ends. Various treatments that produce double-strand breaks induce formation of PALF foci, which fully coincide with γH2AX foci. Thus, PALF and the CYR motif may play important roles in DNA repair of higher eukaryotes.

Original languageEnglish
Pages (from-to)2094-2103
Number of pages10
JournalEMBO Journal
Volume26
Issue number8
DOIs
Publication statusPublished - 2007 Apr 18

Keywords

  • AP endonuclease
  • CYR motif
  • Double-strand breaks
  • PARP1
  • Single-strand breaks

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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