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Molecular and Cellular Biology, October 2007, p. 6733-6741, Vol. 27, No. 19
0270-7306/07/$08.00+0     doi:10.1128/MCB.00961-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Activation of BRCA1/BRCA2-Associated Helicase BACH1 Is Required for Timely Progression through S Phase{triangledown}

Easwari Kumaraswamy and Ramin Shiekhattar*

The Wistar Institute, 3601 Spruce Street Philadelphia, Pennsylvania 19104

Received 31 May 2007/ Returned for modification 26 June 2007/ Accepted 19 July 2007

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.

* Corresponding author. Present address: Center de Regulacio Genomita, Dr. Aiguader, 88, 08003 Barcelona, Spain. Phone: 34-93-316-0230. Fax: 34-93-316-0099. E-mail: ramin.shiekhattar{at}crg.es

{triangledown} Published ahead of print on 30 July 2007.

Molecular and Cellular Biology, October 2007, p. 6733-6741, Vol. 27, No. 19
0270-7306/07/$08.00+0     doi:10.1128/MCB.00961-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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