Nucleic Acids Research Advance Access published online on August 5, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn498
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Genome integrity, repair and replication |
The Bloom's syndrome helicase (BLM) interacts physically and functionally with p12, the smallest subunit of human DNA polymerase 
1Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Winterthurerstr. 190, CH-8057 Zürich, Switzerland, 2Cancer Research UK, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK, 3Department of Biochemistry, 4Department of Molecular Genetics, Faculty of Medicine, Terrence Donnelly Centre for Cellular and Biomolecular Research (dCCBR), University of Toronto, 160 College Street, Toronto ON, Canada, M5S 3E1 and 5Functional Genome Analysis, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany
*To whom correspondence should be addressed. Tel: +1 416 946 78 28; Fax: +1 416 978 82 87; Email: igor.stagljar{at}utoronto.ca
Received April 22, 2008. Revised July 18, 2008. Accepted July 20, 2008.
Bloom's syndrome (BS) is a cancer predisposition disorder caused by mutation of the BLM gene, encoding a member of the RecQ helicase family. Although the phenotype of BS cells is suggestive of a role for BLM in repair of stalled or damaged replication forks, thus far there has been no direct evidence that BLM associates with any of the three human replicative DNA polymerases. Here, we show that BLM interacts specifically in vitro and in vivo with p12, the smallest subunit of human POL 
(hPOL ). The hPOL enzyme, as well as the isolated p12 subunit, stimulates the DNA helicase activity of BLM. Conversely, BLM stimulates hPOL strand displacement activity. Our results provide the first functional link between BLM and the replicative machinery in human cells, and suggest that BLM might be recruited to sites of disrupted replication through an interaction with hPOL . Finally, our data also define a novel role for the poorly characterized p12 subunit of hPOL .
Present address: Nives Selak, Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4058 Basel, Switzerland
The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors