Activation of BRCA1/BRCA2-associated helicase BACH1 is required for timely progression through S phase

Easwari Kumaraswamy, Ramin Shiekhattar

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

BACH1 (also known as FANCJ and BRIP1) is a DNA helicase that directly interacts with the C-terminal BRCT repeat of the breast cancer susceptibility protein BRCA1. Previous biochemical and functional analyses have suggested a role for the BACH1 homolog in Caenorhabditis elegans during DNA replication. Here, we report the association of BACH1 with a distinct BRCA1/BRCA2-containing complex during the S phase of the cell cycle. Depletion of BACH1 or BRCA1 using small interfering RNAs results in delayed entry into the S phase of the cell cycle. Such timely progression through S phase requires the helicase activity of BACH1. Importantly, cells expressing a dominant negative mutation in BACH1 that results in a defective helicase displayed increased activation of DNA damage checkpoints and genomic instability. BACH1 helicase is silenced during the G1 phase of the cell cycle and is activated through a dephosphorylation event as cells enter S phase. These results point to a critical role for BACH1 helicase activity not only in the timely progression through the S phase but also in maintaining genomic stability.

Original languageEnglish (US)
Pages (from-to)6733-6741
Number of pages9
JournalMolecular and cellular biology
Volume27
Issue number19
DOIs
StatePublished - Oct 1 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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