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A conserved Ctp1/CtIP C-terminal peptide stimulates Mre11 endonuclease activity.
Zdravkovic, Aleksandar; Daley, James M; Dutta, Arijit; Niwa, Tatsuya; Murayama, Yasuto; Kanamaru, Shuji; Ito, Kentaro; Maki, Takahisa; Argunhan, Bilge; Takahashi, Masayuki; Tsubouchi, Hideo; Sung, Patrick; Iwasaki, Hiroshi.
Afiliação
  • Zdravkovic A; School and Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Kanagawa 226-8503, Japan.
  • Daley JM; Institute of Innovative Research, Tokyo Institute of Technology, Kanagawa 226-8503, Japan.
  • Dutta A; Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229.
  • Niwa T; Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229.
  • Murayama Y; School and Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Kanagawa 226-8503, Japan.
  • Kanamaru S; Institute of Innovative Research, Tokyo Institute of Technology, Kanagawa 226-8503, Japan.
  • Ito K; Center for Frontier Research, National Institute of Genetics, Shizuoka 411-8540, Japan.
  • Maki T; School and Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Kanagawa 226-8503, Japan.
  • Argunhan B; Institute of Innovative Research, Tokyo Institute of Technology, Kanagawa 226-8503, Japan.
  • Takahashi M; Institute of Innovative Research, Tokyo Institute of Technology, Kanagawa 226-8503, Japan.
  • Tsubouchi H; Institute of Innovative Research, Tokyo Institute of Technology, Kanagawa 226-8503, Japan.
  • Sung P; Institute of Innovative Research, Tokyo Institute of Technology, Kanagawa 226-8503, Japan.
  • Iwasaki H; School and Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Kanagawa 226-8503, Japan.
Proc Natl Acad Sci U S A ; 118(11)2021 03 16.
Article em En | MEDLINE | ID: mdl-33836577
ABSTRACT
The Mre11-Rad50-Nbs1 complex (MRN) is important for repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). The endonuclease activity of MRN is critical for resecting 5'-ended DNA strands at DSB ends, producing 3'-ended single-strand DNA, a prerequisite for HR. This endonuclease activity is stimulated by Ctp1, the Schizosaccharomyces pombe homolog of human CtIP. Here, with purified proteins, we show that Ctp1 phosphorylation stimulates MRN endonuclease activity by inducing the association of Ctp1 with Nbs1. The highly conserved extreme C terminus of Ctp1 is indispensable for MRN activation. Importantly, a polypeptide composed of the conserved 15 amino acids at the C terminus of Ctp1 (CT15) is sufficient to stimulate Mre11 endonuclease activity. Furthermore, the CT15 equivalent from CtIP can stimulate human MRE11 endonuclease activity, arguing for the generality of this stimulatory mechanism. Thus, we propose that Nbs1-mediated recruitment of CT15 plays a pivotal role in the activation of the Mre11 endonuclease by Ctp1/CtIP.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peptídeos / Schizosaccharomyces / Proteínas de Schizosaccharomyces pombe / Proteínas de Ligação a DNA / Exodesoxirribonucleases Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peptídeos / Schizosaccharomyces / Proteínas de Schizosaccharomyces pombe / Proteínas de Ligação a DNA / Exodesoxirribonucleases Idioma: En Ano de publicação: 2021 Tipo de documento: Article