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Cell cycle differences in DNA damage-induced BRCA1 phosphorylation affect its subcellular localization

Shinya Okada1, Toru Ouchi

  • 1Derald H. Ruttenberg Cancer Center, The Mount Sinai School of Medicine, New York University, New York, New York 10029, USA.

The Journal of Biological Chemistry
|November 13, 2002
PubMed

Insights

DNA damage triggers specific BRCA1 protein phosphorylation, altering its cell cycle localization. This study used phospho-specific antibodies to track BRCA1 phosphorylation sites after ionizing radiation (IR) and UV treatments.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • BRCA1 tumor suppressor protein phosphorylation is crucial for cell cycle regulation and DNA damage response.
  • Kinases like ATM/ATR, cdk2, and hChk2 are known to phosphorylate BRCA1.

Purpose of the Study:

  • To investigate BRCA1 phosphorylation at specific serine residues (Ser-988, -1423, -1497, -1524) during S and G2/M phases following DNA damage.
  • To examine the impact of DNA damage on BRCA1 localization and function.

Main Methods:

  • Utilized phospho-Ser-specific antibodies for Ser-988, -1423, -1497, and -1524.
  • Treated cells with ionizing radiation (IR) and UV radiation.
  • Employed confocal microscopy to analyze BRCA1 localization.

Main Results:

  • IR induced Ser-988/Ser-1524 phosphorylation in S phase and Ser-988/Ser-1423 in G2/M phase.
  • UV induced Ser-988 phosphorylation in S phase and Ser-1423 in G2/M phase.
  • Mutant BRCA1 cells showed no phosphorylation at Ser-1423 and -1524; phosphorylation affected BRCA1 localization.

Conclusions:

  • Specific BRCA1 phosphorylation sites are differentially regulated by IR and UV during distinct cell cycle phases.
  • DNA damage-induced BRCA1 phosphorylation alters its subcellular localization, impacting its function.
  • Findings support a model where residue-specific phosphorylation modulates BRCA1's role in DNA repair and cell cycle control.

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