The Bloom's syndrome helicase interacts directly with the human DNA mismatch repair protein hMSH6

Pedrazzi, Graziella, Bachrati, Csanad Z., Selak, Nives , Studer, Ingrid, Petkovic, Maja, Hickson, Ian D., Jiricny, Josef and Stagljar, Igor (2003) The Bloom's syndrome helicase interacts directly with the human DNA mismatch repair protein hMSH6. Biological Chemistry, 384 (8). pp. 1155-1164. ISSN 1431-6730

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Blooms 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 (hMutSα), interacts with the BLM protein both in vivo and in vitro. In agreement with these findings, BLM and hMSH6 colocalise to discrete nuclear foci following exposure of the cells to ionising radiation. However, the purified recombinant MutSα 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 (hMutLα) 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.

Keywords:Bloom syndrome, Mismatch repair, MSH6, BLM, RecQ helicases
Subjects:C Biological Sciences > C700 Molecular Biology, Biophysics and Biochemistry
Divisions:College of Science > School of Life Sciences
ID Code:8889
Deposited On:17 Apr 2013 20:06

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