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

Jacqueline Barlow, Michael Lisby, Rodney Rothstein

Research output: Contribution to journalArticle

129 Citations (Scopus)

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

Fingerprint

Double-Stranded DNA Breaks
Homologous Recombination
S Phase
Cyclin-Dependent Kinase 9
DNA
Endonucleases
Ionizing Radiation
DNA Repair
DNA Damage
Cell Cycle
Proteins

Keywords

  • CELLCYCLE
  • DNA
  • SIGNALING

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Differential Regulation of the Cellular Response to DNA Double-Strand Breaks in G1. / Barlow, Jacqueline; Lisby, Michael; Rothstein, Rodney.

In: Molecular Cell, Vol. 30, No. 1, 11.04.2008, p. 73-85.

Research output: Contribution to journalArticle

Barlow, Jacqueline ; Lisby, Michael ; Rothstein, Rodney. / Differential Regulation of the Cellular Response to DNA Double-Strand Breaks in G1. In: Molecular Cell. 2008 ; Vol. 30, No. 1. pp. 73-85.
@article{c08e75bb938b497d91332cef19e4bdd8,
title = "Differential Regulation of the Cellular Response to DNA Double-Strand Breaks in G1",
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.",
keywords = "CELLCYCLE, DNA, SIGNALING",
author = "Jacqueline Barlow and Michael Lisby and Rodney Rothstein",
year = "2008",
month = "4",
day = "11",
doi = "10.1016/j.molcel.2008.01.016",
language = "English (US)",
volume = "30",
pages = "73--85",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Differential Regulation of the Cellular Response to DNA Double-Strand Breaks in G1

AU - Barlow, Jacqueline

AU - Lisby, Michael

AU - Rothstein, Rodney

PY - 2008/4/11

Y1 - 2008/4/11

N2 - 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.

AB - 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.

KW - CELLCYCLE

KW - DNA

KW - SIGNALING

UR - http://www.scopus.com/inward/record.url?scp=39549114009&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39549114009&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2008.01.016

DO - 10.1016/j.molcel.2008.01.016

M3 - Article

C2 - 18406328

AN - SCOPUS:39549114009

VL - 30

SP - 73

EP - 85

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 1

ER -