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

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 G(1) 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.
Mesh Terms:
Animals, BRCA1 Protein, BRCA2 Protein, Basic-Leucine Zipper Transcription Factors, Caenorhabditis elegans, Chromatin, DNA Damage, Enzyme Activation, Fanconi Anemia Complementation Group Proteins, Humans, Multiprotein Complexes, RNA, Small Interfering, S Phase, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases
Mol. Cell. Biol.
Date: Oct. 01, 2007
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