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BID binds to replication protein A and stimulates ATR function following replicative stress.

Molecular and cellular biology | 2011

Proapoptotic BH3-interacting death domain agonist (BID) regulates apoptosis and the DNA damage response. Following replicative stress, BID associates with proteins of the DNA damage sensor complex, including replication protein A (RPA), ataxia telangiectasia and Rad3 related (ATR), and ATR-interacting protein (ATRIP), and facilitates an efficient DNA damage response. We have found that BID stimulates the association of RPA with components of the DNA damage sensor complex through interaction with the basic cleft of the N-terminal domain of the RPA70 subunit. Disruption of the BID-RPA interaction impairs the association of ATR-ATRIP with chromatin as well as ATR function, as measured by CHK1 activation and recovery of DNA replication following hydroxyurea (HU). We further demonstrate that the association of BID with RPA stimulates the association of ATR-ATRIP to the DNA damage sensor complex. We propose a model in which BID associates with RPA and stimulates the recruitment and/or stabilization of ATR-ATRIP to the DNA damage sensor complex.

Pubmed ID: 21859891 RIS Download

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Associated grants

  • Agency: NIEHS NIH HHS, United States
    Id: P30 ES000267
  • Agency: NIDDK NIH HHS, United States
    Id: P60 DK020593
  • Agency: NIDDK NIH HHS, United States
    Id: DK58404
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK058404
  • Agency: NCI NIH HHS, United States
    Id: 2P30CA068485
  • Agency: NICHD NIH HHS, United States
    Id: P30 HD015052
  • Agency: NEI NIH HHS, United States
    Id: EY08126
  • Agency: NEI NIH HHS, United States
    Id: P30 EY008126
  • Agency: NCI NIH HHS, United States
    Id: P30 CA068485
  • Agency: NCI NIH HHS, United States
    Id: CA68485
  • Agency: NICHD NIH HHS, United States
    Id: HD15052
  • Agency: NIDDK NIH HHS, United States
    Id: DK20593
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL088347
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM065484
  • Agency: NIDDK NIH HHS, United States
    Id: DK59637
  • Agency: NIEHS NIH HHS, United States
    Id: 5P30ES000267
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK020593
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM65484
  • Agency: NIDDK NIH HHS, United States
    Id: U24 DK059637

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