The Bloom's syndrome helicase (BLM) interacts physically and functionally with p12, the smallest subunit of human DNA polymerase delta.
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.
Selak
Nives
N
Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Winterthurerstr. 190, CH-8057 Zürich, Switzerland.
Bachrati
Csanád Z
CZ
Shevelev
Igor
I
Dietschy
Tobias
T
van Loon
Barbara
B
Jacob
Anette
A
Hübscher
Ulrich
U
Hoheisel
Joerg D
JD
Hickson
Ian D
ID
Stagljar
Igor
I
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
D021122:Protein Subunits; C521101:POLD4 protein, human; D004258:DNA Polymerase III; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases