title: The Bloom's syndrome helicase (BLM) interacts physically and functionally with p12, the smallest subunit of human DNA polymerase delta.
abstract: 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 delta (hPOL delta). The hPOL delta enzyme, as well as the isolated p12 subunit, stimulates the DNA helicase activity of BLM. Conversely, BLM stimulates hPOL delta 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 delta. Finally, our data also define a novel role for the poorly characterized p12 subunit of hPOL delta.
authors.affiliation: Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Winterthurerstr. 190, CH-8057 Zürich, Switzerland.
authors.forename: Nives
authors.initials: N
authors.lastname: Selak
authors.forename: Csanád Z
authors.initials: CZ
authors.lastname: Bachrati
authors.forename: Igor
authors.initials: I
authors.lastname: Shevelev
authors.forename: Tobias
authors.initials: T
authors.lastname: Dietschy
authors.forename: Barbara
authors.initials: B
authors.lastname: van Loon
authors.forename: Anette
authors.initials: A
authors.lastname: Jacob
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hübscher
authors.forename: Joerg D
authors.initials: JD
authors.lastname: Hoheisel
authors.forename: Ian D
authors.initials: ID
authors.lastname: Hickson
authors.forename: Igor
authors.initials: I
authors.lastname: Stagljar
mesh_terms: D001665:Binding Sites; D002461:Cell Line, Transformed; D004265:DNA Helicases / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D004258:DNA Polymerase III / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D004261:DNA Replication; D006801:Humans; D021122:Protein Subunits / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D053484:RecQ Helicases
chemical_list: D021122:Protein Subunits; C521101:POLD4 protein, human; D004258:DNA Polymerase III; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases