Article: Regulation of Chromatin Architecture by the PWWP Domain-Containing DNA Damage-Responsive Factor EXPAND1/MUM1

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TitleRegulation of Chromatin Architecture by the PWWP Domain-Containing DNA Damage-Responsive Factor EXPAND1/MUM1
AuthorsHuen, MSY1
Huang, J
Leung, JWC
Sy, SMH
Leung, KM
Ching, YP1
Tsao, SW1
Chen, J
KeywordsDNA
Issue Date2010
PublisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/molcel
CitationMolecular Cell, 2010, v. 37 n. 6, p. 854-864 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.molcel.2009.12.040
AbstractDynamic 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. © 2010 Elsevier Inc. All rights reserved.
ISSN1097-2765
2011 Impact Factor: 14.178
2011 SCImago Journal Rankings: 4.574
DOIhttp://dx.doi.org/10.1016/j.molcel.2009.12.040
ISI Accession Number IDWOS:000276135100012
Funding AgencyGrant Number
National Institutes of HealthCA089239
CA092312
CA100109
Department of Anatomy, HKU
HKU200908159008
Department of Defense
Funding Information:

This work was supported in part by grants from the National Institutes of Health (CA089239, CA092312, and CA100109 to J.C.), from Startup Fund (Department of Anatomy, HKU to M.S.Y.H.) and Seed Funding for Basic Research (Project Code 200908159008; HKU to M.S.Y.H.). M.S.Y.H. would like to thank Drs. Zhiwei Chen and Henggui Liu (AIDS Institute, HKU) for help with flow cytometry analysis and is grateful to J.C. for his continuous support and mentoring. J.C is a recipient of an Era of Hope Scholar award from the Department of Defense and is a member of the Mayo Clinic Breast SPORE Program (P50 CA116201).

ReferencesReferences in Scopus
GrantsFunctional characterisation of EXPAND1 and its role in the maintenance of genome stability and tumor suppression.
DC Field
Value
dc.contributor.authorHuen, MSY
dc.contributor.authorHuang, J
dc.contributor.authorLeung, JWC
dc.contributor.authorSy, SMH
dc.contributor.authorLeung, KM
dc.contributor.authorChing, YP
dc.contributor.authorTsao, SW
dc.contributor.authorChen, J
dc.date.accessioned2010-09-06T05:55:38Z
dc.date.available2010-09-06T05:55:38Z
dc.date.issued2010
dc.description.abstractDynamic 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. © 2010 Elsevier Inc. All rights reserved.
dc.description.grantFunctional characterisation of EXPAND1 and its role in the maintenance of genome stability and tumor suppression.
dc.description.grantcode100909
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationMolecular Cell, 2010, v. 37 n. 6, p. 854-864 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.molcel.2009.12.040
dc.identifier.citeulike6959115
dc.identifier.doihttp://dx.doi.org/10.1016/j.molcel.2009.12.040
dc.identifier.epage864
dc.identifier.hkuros169512
dc.identifier.isiWOS:000276135100012
Funding AgencyGrant Number
National Institutes of HealthCA089239
CA092312
CA100109
Department of Anatomy, HKU
HKU200908159008
Department of Defense
Funding Information:

This work was supported in part by grants from the National Institutes of Health (CA089239, CA092312, and CA100109 to J.C.), from Startup Fund (Department of Anatomy, HKU to M.S.Y.H.) and Seed Funding for Basic Research (Project Code 200908159008; HKU to M.S.Y.H.). M.S.Y.H. would like to thank Drs. Zhiwei Chen and Henggui Liu (AIDS Institute, HKU) for help with flow cytometry analysis and is grateful to J.C. for his continuous support and mentoring. J.C is a recipient of an Era of Hope Scholar award from the Department of Defense and is a member of the Mayo Clinic Breast SPORE Program (P50 CA116201).

dc.identifier.issn1097-2765
2011 Impact Factor: 14.178
2011 SCImago Journal Rankings: 4.574
dc.identifier.issue6
dc.identifier.openurl
dc.identifier.pmid20347427
dc.identifier.scopuseid_2-s2.0-77949708459
dc.identifier.spage854
dc.identifier.urihttp://hdl.handle.net/10722/67495
dc.identifier.volume37
dc.languageeng
dc.publisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/molcel
dc.publisher.placeUnited States
dc.relation.ispartofMolecular Cell
dc.relation.referencesReferences in Scopus
dc.subject.meshAmino Acid Sequence
dc.subject.meshAnimals
dc.subject.meshChromatin - genetics - metabolism
dc.subject.meshChromosomal Proteins, Non-Histone - chemistry - genetics - metabolism
dc.subject.meshDNA Damage
dc.subjectDNA
dc.titleRegulation of Chromatin Architecture by the PWWP Domain-Containing DNA Damage-Responsive Factor EXPAND1/MUM1
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. University of Texas M. D. Anderson Cancer Center