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Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control double-strand break repair by

Oliver Limbo1, Charly Chahwan, Yoshiki Yamada

  • 1Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Molecular Cell
|October 16, 2007
PubMed

Insights

Fission yeast Ctp1 is recruited to DNA double-strand breaks (DSBs) and aids in homologous recombination (HR) repair. Its cell-cycle-regulated expression suggests Ctp1 controls HR during DNA replication.

Area of Science:

  • Molecular Biology
  • Cell Cycle Regulation
  • DNA Repair

Background:

  • The Mre11-Rad50-Nbs1 (MRN) complex senses DNA double-strand breaks (DSBs) and initiates homologous recombination (HR) repair.
  • Homologous recombination (HR) is repressed in G1 phase, favoring nonhomologous end-joining (NHEJ) for DSB repair.
  • The mechanisms controlling cell-cycle-specific HR regulation remain largely unknown.

Purpose of the Study:

  • To investigate the role of fission yeast Ctp1 in DNA double-strand break (DSB) repair and cell-cycle control.
  • To elucidate the function of Ctp1 in homologous recombination (HR) and its relationship with the MRN complex.

Main Methods:

  • Characterization of Ctp1 recruitment to DSBs in fission yeast.
  • Assessment of Ctp1's requirement for RPA-coated single-strand DNA formation.
  • Analysis of ctp1(+) gene transcription patterns throughout the cell cycle.

Main Results:

  • Fission yeast Ctp1 is recruited to DSBs and is essential for HR repair.
  • Ctp1 facilitates the formation of RPA-coated single-strand DNA, indicating a role in MRN-mediated 5' to 3' resection.
  • Ctp1 expression is periodic, coinciding with the onset of DNA replication.

Conclusions:

  • Ctp1 is a key mediator of homologous recombination (HR) in fission yeast.
  • Ctp1 functions with the MRN complex to promote DNA resection at DSBs.
  • Cell-cycle-dependent regulation of Ctp1 expression underlies the control of HR during the cell cycle.

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