Record number :
Title of article :
RNF168 Binds and Amplifies Ubiquitin Conjugates on Damaged Chromosomes to Allow Accumulation of Repair Proteins
Author/Authors :
Carsten Doil، نويسنده , , Niels Mailand، نويسنده , , Simon Bekker-Jensen، نويسنده , , Patrice Menard، نويسنده , , Dorthe Helena Larsen، نويسنده , , Rainer Pepperkok، نويسنده , , Jan Ellenberg، نويسنده , , Stephanie Panier، نويسنده , , Daniel Durocher، نويسنده , , Jiri Bartek، نويسنده , , Jiri Lukas، نويسنده , , Claudia Lukas، نويسنده ,
Issue Information :
هفته نامه با شماره پیاپی سال 2009
Pages :
From page :
To page :
Abstract :
DNA double-strand breaks (DSBs) not only interrupt the genetic information, but also disrupt the chromatin structure, and both impairments require repair mechanisms to ensure genome integrity. We showed previously that RNF8-mediated chromatin ubiquitylation protects genome integrity by promoting the accumulation of repair factors at DSBs. Here, we provide evidence that, while RNF8 is necessary to trigger the DSB-associated ubiquitylations, it is not sufficient to sustain conjugated ubiquitin in this compartment. We identified RNF168 as a novel chromatin-associated ubiquitin ligase with an ability to bind ubiquitin. We show that RNF168 interacts with ubiquitylated H2A, assembles at DSBs in an RNF8-dependent manner, and, by targeting H2A and H2AX, amplifies local concentration of lysine 63-linked ubiquitin conjugates to the threshold required for retention of 53BP1 and BRCA1. Thus, RNF168 defines a new pathway involving sequential ubiquitylations on damaged chromosomes and uncovers a functional cooperation between E3 ligases in genome maintenance.
Journal title :
Serial Year :
Link To Document :