TRIP12 and UBR5 Suppress Spreading of Chromatin Ubiquitylation at Damaged Chromosomes

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F12%3A33140876" target="_blank" >RIV/61989592:15110/12:33140876 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1016/j.cell.2012.06.039" target="_blank" >http://dx.doi.org/10.1016/j.cell.2012.06.039</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cell.2012.06.039" target="_blank" >10.1016/j.cell.2012.06.039</a>

Result language

angličtina

Original language name

TRIP12 and UBR5 Suppress Spreading of Chromatin Ubiquitylation at Damaged Chromosomes

Original language description

Histone ubiquitylation is a prominent response to DNA double-strand breaks (DSBs), but how these modifications are confined to DNA lesions is not understood. Here, we show that TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage. We find that RNF168 can be saturated by increasing amounts of DSBs. Depletion of TRIP12 and UBR5 allows accumulation of RNF168 to supra-physiological levels,followed by massive spreading of ubiquitin conjugates and hyperaccumulation of ubiquitin-regulated genome caretakers such as 53BP1 and BRCA1. Thus, regulatory and proteolytic ubiquitylations are wired in a self-limiting circuit that promotes histone ubiquitylation near the DNA lesions but at the same time counteracts its excessive spreading to undamaged chromosomes. We provide evidence that this mechanism is vital for the homeostasis of ubiquitin-controlled events after DNA breakage and

Czech name

—

Czech description

—

Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FD - Oncology and haematology

OECD FORD branch

—

Project

<a href="/en/project/ED0030%2F01%2F01" target="_blank" >ED0030/01/01: Biomedicine for regional development and human resources</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2012

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cell

ISSN

0092-8674

e-ISSN

—

Volume of the periodical

150

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

697-709

UT code for WoS article

000308002300006

EID of the result in the Scopus database

—