Differential Regulation of the Cellular Response to DNA Double-Strand Breaks in G1

Jacqueline Barlow, Michael Lisby, Rodney Rothstein

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

Double-strand breaks (DSBs) are potentially lethal DNA lesions that can be repaired by either homologous recombination (HR) or nonhomologous end-joining (NHEJ). We show that DSBs induced by ionizing radiation (IR) are efficiently processed for HR and bound by Rfa1 during G1, while endonuclease-induced breaks are recognized by Rfa1 only after the cell enters S phase. This difference is dependent on the DNA end-binding Yku70/Yku80 complex. Cell-cycle regulation is also observed in the DNA damage checkpoint response. Specifically, the 9-1-1 complex is required in G1 cells to recruit the Ddc2 checkpoint protein to damaged DNA, while, upon entry into S phase, the cyclin-dependent kinase Cdc28 and the 9-1-1 complex both serve to recruit Ddc2 to foci. Together, these results demonstrate that the DNA repair machinery distinguishes between different types of damage in G1, which translates into different modes of checkpoint activation in G1 and S/G2 cells.

Original languageEnglish (US)
Pages (from-to)73-85
Number of pages13
JournalMolecular Cell
Volume30
Issue number1
DOIs
StatePublished - Apr 11 2008
Externally publishedYes

Keywords

  • CELLCYCLE
  • DNA
  • SIGNALING

ASJC Scopus subject areas

  • Molecular Biology

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