The Bloom's syndrome helicase interacts directly with the human DNA mismatch repair protein hMSH6.
Bloom's syndrome (BS) is a rare genetic disorder characterised by genome instability and cancer susceptibility. BLM, the BS gene product, belongs to the highly-conserved RecQ family of DNA helicases. Although the exact function of BLM in human cells remains to be defined, it seems likely that BLM eliminates some form of homologous recombination (HR) intermediate that arises during DNA replication. Similarly, the mismatch repair (MMR) system also plays a crucial role in the maintenance of genomic stability, by correcting DNA errors generated during DNA replication. Recent evidence implicates components of the MMR system also in HR repair. We now show that hMSH6, a component of the heterodimeric mismatch recognition complex hMSH2/hMSH6 (hMutS(alpha)), interacts with the BLM protein both in vivo and in vitro. In agreement with these findings, BLM and hMSH6 co-localise to discrete nuclear foci following exposure of the cells to ionising radiation. However, the purified recombinant MutS(alpha) complex does not affect the helicase activity of BLM in vitro. As BLM has previously been shown to interact with the hMLH1 component of the hMLH1/hPMS2 (hMutL(alpha)) heterodimeric MMR complex, our present findings further strengthen the link between BLM and processes involving correction of DNA mismatches, such as in the regulation of the fidelity of homologous recombination events.
Pedrazzi
Graziella
G
Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Winterthurerstr. 190, CH-8057 Zürich, Switzerland.
Bachrati
Csanád Z
CZ
Selak
Nives
N
Studer
Ingrid
I
Petkovic
Maja
M
Hickson
Ian D
ID
Jiricny
Josef
J
Stagljar
Igor
I
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D020137:Base Pair Mismatch; D001816:Bloom Syndrome / Q000201:enzymology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D053484:RecQ Helicases
D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D046911:Macromolecular Substances; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases