The Bloom's syndrome protein (BLM) interacts with MLH1 but is not required for DNA mismatch repair.
Bloom's syndrome (BS) is a rare autosomal recessive disorder characterized by pre- and postnatal growth deficiency, immunodeficiency, and a tremendous predisposition to a wide variety of cancers. Cells from BS individuals are characterized by a high incidence of chromosomal gaps and breaks, elevated sister chromatid exchange, quadriradial formations, and locus-specific mutations. BS is the consequence of mutations that lead to loss of function of BLM, a gene encoding a helicase with homology to the RecQ helicase family. To delineate the role of BLM in DNA replication, recombination, and repair we used a yeast two-hybrid screen to identify potential protein partners of the BLM helicase. The C terminus of BLM interacts directly with MLH1 in the yeast-two hybrid assay; far Western analysis and co-immunoprecipitations confirmed the interaction. Cell extracts deficient in BLM were competent for DNA mismatch repair. These data suggest that the BLM helicase and MLH1 function together in replication, recombination, or DNA repair events independent of single base mismatch repair.
Langland
G
G
Department of Molecular Genetics, Biochemistry, and Microbiology and the Howard Hughes Medical Institute, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Kordich
J
J
Creaney
J
J
Goss
K H
KH
Lillard-Wetherell
K
K
Bebenek
K
K
Kunkel
T A
TA
Groden
J
J
D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D020137:Base Pair Mismatch; D015153:Blotting, Western; D002352:Carrier Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D004265:DNA Helicases / Q000737:chemistry / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D008297:Male; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D011233:Precipitin Tests; D011485:Protein Binding; D053484:RecQ Helicases; D011995:Recombination, Genetic; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; C506725:RECQL protein, human; D000070957:MutL Protein Homolog 1; D004265:DNA Helicases; D053484:RecQ Helicases