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PMID: 20347427 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Regulation of chromatin architecture by the PWWP domain-containing DNA damage-responsive factor EXPAND1/MUM1.

Molecular cell ·Vol. 37 ·No. 6 ·2010-03-26 ·Pages 854-64

Huen MS, Huang J, Leung JW, Sy SM, Leung KM, Ching YP, Tsao SW, Chen J

Abstract

Dynamic changes of chromatin structure facilitate diverse biological events, including DNA replication, repair, recombination, and gene transcription. Recent evidence revealed that DNA damage elicits alterations to the chromatin to facilitate proper checkpoint activation and DNA repair. Here we report the identification of the PWWP domain-containing protein EXPAND1/MUM1 as an architectural component of the chromatin, which in response to DNA damage serves as an accessory factor to promote cell survival. Depletion of EXPAND1/MUM1 or inactivation of its PWWP domain resulted in chromatin compaction. Upon DNA damage, EXPAND1/MUM1 rapidly concentrates at the vicinity of DNA damage sites via its direct interaction with 53BP1. Ablation of this interaction impaired damage-induced chromatin decondensation, which is accompanied by sustained DNA damage and hypersensitivity to genotoxic stress. Collectively, our study uncovers a chromatin-bound factor that serves an accessory role in coupling damage signaling with chromatin changes in response to DNA damage.

MeSH Terms
Amino Acid Sequence Animals Cell Survival Cells, Cultured Chromatin/genetics,metabolism Chromosomal Proteins, Non-Histone/chemistry,genetics,metabolism DNA Damage DNA-Binding Proteins Humans Intracellular Signaling Peptides and Proteins/deficiency,metabolism Mice Molecular Sequence Data RNA, Small Interfering/genetics Response Elements Signal Transduction Tumor Suppressor p53-Binding Protein 1
Chemicals
Chromatin Chromosomal Proteins, Non-Histone DNA-Binding Proteins Intracellular Signaling Peptides and Proteins PWWP3A protein, human RNA, Small Interfering Trp53bp1 protein, mouse Tumor Suppressor p53-Binding Protein 1
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Huen Michael S Y
Department of Anatomy, The University of Hong Kong, L1, Laboratory Block, 21 Sassoon Road, Hong Kong SAR. huen.michael@hku.hk
Huang Jun
Leung Justin W C
Sy Shirley M-H
Leung Ka Man
Ching Yick-Pang
Tsao Sai Wah
Chen Junjie
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2009.12.040
Email
huen.michael@hku.hk
Published
2010-03-26
Pages
854-64
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC3695488
Subset
IM
Grants
NCI NIH HHS · R01 CA089239-09 · United States
NCI NIH HHS · R01 CA092312 · United States
NCI NIH HHS · R01 CA100109 · United States
NCI NIH HHS · R01 CA100109-07 · United States
NCI NIH HHS · R01 CA089239-11 · United States
NCI NIH HHS · CA092312 · United States
NCI NIH HHS · P50 CA116201 · United States
NCI NIH HHS · CA100109 · United States
NCI NIH HHS · R01 CA092312-09 · United States
NCI NIH HHS · CA089239 · United States
NCI NIH HHS · R01 CA089239 · United States
NCI NIH HHS · R01 CA100109-08 · United States
NCI NIH HHS · R01 CA092312-11 · United States
NCI NIH HHS · R01 CA100109-09 · United States
NCI NIH HHS · R01 CA092312-10 · United States
NCI NIH HHS · R01 CA089239-10 · United States
External Links
PubMed source DOI: 10.1016/j.molcel.2009.12.040 PMC Full Text View journal details
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