Direct involvement of retinoblastoma family proteins in DNA repair by non-homologous end-joining
Standard
Direct involvement of retinoblastoma family proteins in DNA repair by non-homologous end-joining. / Cook, Rebecca; Zoumpoulidou, Georgia; Luczynski, Maciej T; Rieger, Simone; Moquet, Jayne; Spanswick, Victoria J; Hartley, John A; Rothkamm, Kai; Huang, Paul H; Mittnacht, Sibylle.
in: CELL REP, Jahrgang 10, Nr. 12, 31.03.2015, S. 2006-18.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Direct involvement of retinoblastoma family proteins in DNA repair by non-homologous end-joining
AU - Cook, Rebecca
AU - Zoumpoulidou, Georgia
AU - Luczynski, Maciej T
AU - Rieger, Simone
AU - Moquet, Jayne
AU - Spanswick, Victoria J
AU - Hartley, John A
AU - Rothkamm, Kai
AU - Huang, Paul H
AU - Mittnacht, Sibylle
N1 - Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2015/3/31
Y1 - 2015/3/31
N2 - Deficiencies in DNA double-strand break (DSB) repair lead to genetic instability, a recognized cause of cancer initiation and evolution. We report that the retinoblastoma tumor suppressor protein (RB1) is required for DNA DSB repair by canonical non-homologous end-joining (cNHEJ). Support of cNHEJ involves a mechanism independent of RB1's cell-cycle function and depends on its amino terminal domain with which it binds to NHEJ components XRCC5 and XRCC6. Cells with engineered loss of RB family function as well as cancer-derived cells with mutational RB1 loss show substantially reduced levels of cNHEJ. RB1 variants disabled for the interaction with XRCC5 and XRCC6, including a cancer-associated variant, are unable to support cNHEJ despite being able to confer cell-cycle control. Our data identify RB1 loss as a candidate driver of structural genomic instability and a causative factor for cancer somatic heterogeneity and evolution.
AB - Deficiencies in DNA double-strand break (DSB) repair lead to genetic instability, a recognized cause of cancer initiation and evolution. We report that the retinoblastoma tumor suppressor protein (RB1) is required for DNA DSB repair by canonical non-homologous end-joining (cNHEJ). Support of cNHEJ involves a mechanism independent of RB1's cell-cycle function and depends on its amino terminal domain with which it binds to NHEJ components XRCC5 and XRCC6. Cells with engineered loss of RB family function as well as cancer-derived cells with mutational RB1 loss show substantially reduced levels of cNHEJ. RB1 variants disabled for the interaction with XRCC5 and XRCC6, including a cancer-associated variant, are unable to support cNHEJ despite being able to confer cell-cycle control. Our data identify RB1 loss as a candidate driver of structural genomic instability and a causative factor for cancer somatic heterogeneity and evolution.
U2 - 10.1016/j.celrep.2015.02.059
DO - 10.1016/j.celrep.2015.02.059
M3 - SCORING: Journal article
C2 - 25818292
VL - 10
SP - 2006
EP - 2018
JO - CELL REP
JF - CELL REP
SN - 2211-1247
IS - 12
ER -