EZH2 promotes degradation of stalled replication forks by recruiting MUS81 through histone H3 trimethylation

Rondinelli et al. show that EZH2-mediated H3K27me3 at stalled replication forks recruits MUS81 nuclease to facilitate fork degradation. Loss of EZH2 contributes to PARPi resistance in BRCA2-deficient tumours. The emergence of resistance to poly-ADP-ribose polymerase inhibitors (PARPi) poses a threat...

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Bibliographic Details
Published in:	Nature cell biology Vol. 19; no. 11; pp. 1371 - 1378
Main Authors:	Rondinelli, Beatrice, Gogola, Ewa, Yücel, Hatice, Duarte, Alexandra A., van de Ven, Marieke, van der Sluijs, Roxanne, Konstantinopoulos, Panagiotis A., Jonkers, Jos, Ceccaldi, Raphaël, Rottenberg, Sven, D’Andrea, Alan D.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01.11.2017 Nature Publishing Group
Subjects:	42/89 45/61 631/337/100/2285 631/337/1427 631/67 64/60 82/29 96/1 Adenosine diphosphate Analysis Animals Biomarkers Biomarkers, Tumor - metabolism BRCA mutations BRCA1 protein BRCA1 Protein - metabolism BRCA2 protein BRCA2 Protein - metabolism Breast cancer Breast Neoplasms - genetics Breast Neoplasms - metabolism Cancer Cancer Research Cell Biology Cell Line Cell Line, Tumor Chemoresistance Chemotherapy Control stability Deoxyribonucleic acid Developmental Biology DNA DNA biosynthesis DNA damage DNA replication DNA Replication - drug effects DNA Replication - genetics DNA-Binding Proteins - metabolism Drug Resistance, Neoplasm - genetics Endonucleases - metabolism Enhancer of Zeste Homolog 2 Protein - metabolism Female Genetic aspects Genomic Instability - drug effects Genomic Instability - genetics Genomics HEK293 Cells HeLa Cells Histone H3 Histones Histones - metabolism Humans letter Life Sciences Methylation Methylation - drug effects Mice Mice, Nude Nuclease Patient outcomes Physiological aspects Poly(ADP-ribose) Polymerase Inhibitors - pharmacology Recruitment Replication Replication forks Ribose Stabilization Stem Cells Tumors United States
ISSN:	1465-7392, 1476-4679, 1476-4679
Online Access:	Get full text
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