title: Evidence for a direct association of hMRE11 with the human mismatch repair protein hMLH1.
abstract: In both mitotic and meiotic processes, cellular surveillance of the integrity of genetic information transmission from parental cells to their subsequent generations is carried out by a network of proteins primarily involved in cell-cycle regulation, DNA replication, DNA repair, and chromosome segregation. Within this context, the mammalian MRE11 represents an essential multifunctional protein that promotes repair of DNA double-strand breaks and plays a role in the signaling of DNA damage response. Mutations in human hMRE11 gene could contribute to the rare "AT-like" disorder. However, at present time the functional roles of hMRE11 in these cellular processes are elusive. In the current study, we provide evidence that hMRE11 interacts physically with the mismatch repair protein hMLH1 through yeast two-hybrid analysis. In addition, we show that recombinant hMRE11 and hMLH1 proteins interact when these two proteins are coexpressed in bacterial cells, and both proteins can be co-immunoprecipitated from human cell extracts. Furthermore, hMRE11 and hMLH1 display similar expression patterns when examined with a human normal/tumor DNA array. Together, these data suggest that hMRE11 and hMLH1 might act in a co-operative fashion during DNA damage detection, signaling, and repair.
authors.affiliation: School of Molecular Biosciences, Center for Reproductive Biology, P.O. Box 644660, Washington State University, Pullman, WA 99164-4660, USA. cher@wsu.edu
authors.forename: Chengtao
authors.initials: C
authors.lastname: Her
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Vo
authors.forename: Xiling
authors.initials: X
authors.lastname: Wu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020137:Base Pair Mismatch; D015153:Blotting, Western; D002352:Carrier Proteins; D002460:Cell Line; D004249:DNA Damage / Q000235:genetics; D004252:DNA Mutational Analysis; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D000076228:MRE11 Homologue Protein; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D011233:Precipitin Tests; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; C121766:MRE11 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D000076228:MRE11 Homologue Protein; D000070957:MutL Protein Homolog 1