The Bloom's Syndrome Helicase Interacts Directly with the Human DNA Mismatch Repair Protein hMSH6
- 20 January 2003
- journal article
- research article
- Published by Walter de Gruyter GmbH in Biological Chemistry
- Vol. 384 (8) , 1155-1164
- https://doi.org/10.1515/bc.2003.128
Abstract
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
This publication has 49 references indexed in Scilit:
- The Processing of Holliday Junctions by BLM and WRN Helicases Is Regulated by p53Journal of Biological Chemistry, 2002
- The Bloom syndrome protein interacts and cooperates with p53 in regulation of transcription and cell growth controlOncogene, 2001
- Functional interactions and signaling properties of mammalian DNA mismatch repair proteinsCell Death & Differentiation, 2001
- The Bloom's Syndrome Protein (BLM) Interacts with MLH1 but Is Not Required for DNA Mismatch RepairJournal of Biological Chemistry, 2001
- Potential Role for the BLM Helicase in Recombinational Repair via a Conserved Interaction with RAD51Journal of Biological Chemistry, 2001
- hMSH3 and hMSH6 interact with PCNA and colocalize with it to replication fociGenes & Development, 2001
- Binding and Melting of D-Loops by the Bloom Syndrome HelicaseBiochemistry, 2000
- The Bloom's Syndrome Helicase Unwinds G4 DNAJournal of Biological Chemistry, 1998
- GTBP, a 160-Kilodalton Protein Essential for Mismatch-binding Activity in Human CellsScience, 1995
- Bloom SyndromeMedicine, 1993