The chromatin remodeling protein BRG1 modulates BRCA1 response to UV irradiation by regulating ATR/ATM activation

Ling Zhang, Hua Chen, Ming Gong, Feng Gong

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The SWI/SNF chromatin remodeling complex plays a role in the repair of UV-induced DNA damage. It was proposed that chromatin remodeling activities are utilized to increase the accessibility of nucleotide excision repair (NER) machinery and checkpoint factors to the damaged DNA. It was shown recently that BRCA1 contributes to UV damage response by promoting photoproduct excision, triggering post-UV checkpoint activation and post-replicative repair. In this study, we show that BRCA1 rapidly binds to UV damage sites when cells are undergoing DNA synthesis. In contrast, two phosphorylated forms of BRCA1 do not accumulate at sites of UV damage. Depletion of BRG1, a core subunit of the human SWI/SNF-BAF complex, impairs the recruitment of BRCA1 to the damage sites and attenuates DNA damage induced BRCA1 phosphorylation. At UV lesions-stalled replication forks, BRG1 promotes RPA phosphorylation in response to UV irradiation, since UV-induced phosphorylation of chromatin bound RPA drops significantly when BRG1 is depleted in human cells. Importantly, activation of the ATM/ATR kinases is attenuated when BRG1 is depleted. We propose that BRG1 modulates BRCA1 response to UV irradiation by regulating ATM/ATR activation.

Original languageEnglish
Article numberArticle 00007
JournalFrontiers in Oncology
Volume3 JAN
DOIs
StatePublished - Dec 24 2013

Fingerprint

Chromatin Assembly and Disassembly
Phosphorylation
DNA Damage
Proteins
DNA
DNA Repair
Chromatin
Phosphotransferases

Keywords

  • ATR/ATM
  • BRCA1
  • BRG1
  • DNA damage response
  • Nucleotide excision repair
  • RPA
  • SWI/SNF
  • UV irradiation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The chromatin remodeling protein BRG1 modulates BRCA1 response to UV irradiation by regulating ATR/ATM activation. / Zhang, Ling; Chen, Hua; Gong, Ming; Gong, Feng.

In: Frontiers in Oncology, Vol. 3 JAN, Article 00007, 24.12.2013.

Research output: Contribution to journalArticle

@article{24288494af30452c85e504dc62d969d8,
title = "The chromatin remodeling protein BRG1 modulates BRCA1 response to UV irradiation by regulating ATR/ATM activation",
abstract = "The SWI/SNF chromatin remodeling complex plays a role in the repair of UV-induced DNA damage. It was proposed that chromatin remodeling activities are utilized to increase the accessibility of nucleotide excision repair (NER) machinery and checkpoint factors to the damaged DNA. It was shown recently that BRCA1 contributes to UV damage response by promoting photoproduct excision, triggering post-UV checkpoint activation and post-replicative repair. In this study, we show that BRCA1 rapidly binds to UV damage sites when cells are undergoing DNA synthesis. In contrast, two phosphorylated forms of BRCA1 do not accumulate at sites of UV damage. Depletion of BRG1, a core subunit of the human SWI/SNF-BAF complex, impairs the recruitment of BRCA1 to the damage sites and attenuates DNA damage induced BRCA1 phosphorylation. At UV lesions-stalled replication forks, BRG1 promotes RPA phosphorylation in response to UV irradiation, since UV-induced phosphorylation of chromatin bound RPA drops significantly when BRG1 is depleted in human cells. Importantly, activation of the ATM/ATR kinases is attenuated when BRG1 is depleted. We propose that BRG1 modulates BRCA1 response to UV irradiation by regulating ATM/ATR activation.",
keywords = "ATR/ATM, BRCA1, BRG1, DNA damage response, Nucleotide excision repair, RPA, SWI/SNF, UV irradiation",
author = "Ling Zhang and Hua Chen and Ming Gong and Feng Gong",
year = "2013",
month = "12",
day = "24",
doi = "10.3389/fonc.2013.00007",
language = "English",
volume = "3 JAN",
journal = "Frontiers in Oncology",
issn = "2234-943X",
publisher = "Frontiers Media S. A.",

}

TY - JOUR

T1 - The chromatin remodeling protein BRG1 modulates BRCA1 response to UV irradiation by regulating ATR/ATM activation

AU - Zhang, Ling

AU - Chen, Hua

AU - Gong, Ming

AU - Gong, Feng

PY - 2013/12/24

Y1 - 2013/12/24

N2 - The SWI/SNF chromatin remodeling complex plays a role in the repair of UV-induced DNA damage. It was proposed that chromatin remodeling activities are utilized to increase the accessibility of nucleotide excision repair (NER) machinery and checkpoint factors to the damaged DNA. It was shown recently that BRCA1 contributes to UV damage response by promoting photoproduct excision, triggering post-UV checkpoint activation and post-replicative repair. In this study, we show that BRCA1 rapidly binds to UV damage sites when cells are undergoing DNA synthesis. In contrast, two phosphorylated forms of BRCA1 do not accumulate at sites of UV damage. Depletion of BRG1, a core subunit of the human SWI/SNF-BAF complex, impairs the recruitment of BRCA1 to the damage sites and attenuates DNA damage induced BRCA1 phosphorylation. At UV lesions-stalled replication forks, BRG1 promotes RPA phosphorylation in response to UV irradiation, since UV-induced phosphorylation of chromatin bound RPA drops significantly when BRG1 is depleted in human cells. Importantly, activation of the ATM/ATR kinases is attenuated when BRG1 is depleted. We propose that BRG1 modulates BRCA1 response to UV irradiation by regulating ATM/ATR activation.

AB - The SWI/SNF chromatin remodeling complex plays a role in the repair of UV-induced DNA damage. It was proposed that chromatin remodeling activities are utilized to increase the accessibility of nucleotide excision repair (NER) machinery and checkpoint factors to the damaged DNA. It was shown recently that BRCA1 contributes to UV damage response by promoting photoproduct excision, triggering post-UV checkpoint activation and post-replicative repair. In this study, we show that BRCA1 rapidly binds to UV damage sites when cells are undergoing DNA synthesis. In contrast, two phosphorylated forms of BRCA1 do not accumulate at sites of UV damage. Depletion of BRG1, a core subunit of the human SWI/SNF-BAF complex, impairs the recruitment of BRCA1 to the damage sites and attenuates DNA damage induced BRCA1 phosphorylation. At UV lesions-stalled replication forks, BRG1 promotes RPA phosphorylation in response to UV irradiation, since UV-induced phosphorylation of chromatin bound RPA drops significantly when BRG1 is depleted in human cells. Importantly, activation of the ATM/ATR kinases is attenuated when BRG1 is depleted. We propose that BRG1 modulates BRCA1 response to UV irradiation by regulating ATM/ATR activation.

KW - ATR/ATM

KW - BRCA1

KW - BRG1

KW - DNA damage response

KW - Nucleotide excision repair

KW - RPA

KW - SWI/SNF

KW - UV irradiation

UR - http://www.scopus.com/inward/record.url?scp=84884510464&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884510464&partnerID=8YFLogxK

U2 - 10.3389/fonc.2013.00007

DO - 10.3389/fonc.2013.00007

M3 - Article

AN - SCOPUS:84884510464

VL - 3 JAN

JO - Frontiers in Oncology

JF - Frontiers in Oncology

SN - 2234-943X

M1 - Article 00007

ER -