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  • The EMBO Journal (2007) 26, 2094 - 2103
  • doi:10.1038/sj.emboj.7601663

Published online: 29 March 2007

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

Shin-ichiro Kanno1,2, Hiroyuki Kuzuoka1, Shigeru Sasao1, Zehui Hong1, Li Lan1, Satoshi Nakajima1 and Akira Yasui1

  1. Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Aobaku, Sendai, Japan
  2. Japan Bio Services Co., Ltd, Asaka, Saitama, Japan

Correspondence to:

Akira Yasui, Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aobaku, Sendai 980-8575, Japan. Tel.: +81 22 717 8465; Fax: +81 22 717 8470; E-mail: ayasui@idac.tohoku.ac.jp

Shin-ichiro Kanno, Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aobaku, Sendai 980-8575, Japan. Tel.: +81 22 717 8469; Fax: +81 22 717 8470; E-mail: ranmaru@idac.tohoku.ac.jp

Received 22 September 2006; Accepted 5 March 2007

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 gammaH2AX foci. Thus, PALF and the CYR motif may play important roles in DNA repair of higher eukaryotes.

  • Keywords:

    • AP endonuclease,
    • CYR motif,
    • double-strand breaks,
    • PARP1,
    • single-strand breaks