Evidence that hMLH3 functions primarily in meiosis and in hMSH2-hMSH3 mismatch repair.
The MutS (MSH) and MutL (MLH) homologs are conserved proteins that function in mismatch repair (MMR) and meiosis. We examined mRNA and protein expression of hMLH3 compared to other human MSH and MLH in a panel of human tissues and the HeLa cell line. Quantitative PCR suggests that MSH and MLH transcripts are expressed ubiquitously. hMLH3 mRNA is present at low levels in numerous tissues. Protein expression appears to correlate with a threshold of mRNA expression with hMLH3 present at high levels in testis. In addition, we have found and mapped interactions between hMLH1 and hMLH3 with hMSH3. These data are consistent with yeast studies and suggest a role for hMLH3 in meiosis as well as hMSH2-hMSH3 repair processes and little if any role in Hereditary Non-Polyposis Colorectal Cancer (HNPCC).
Charbonneau
Nicole
N
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Columbus, OH, USA.
Amunugama
Ravindra
R
Schmutte
Christoph
C
Yoder
Kristine
K
Fishel
Richard
R
D002352:Carrier Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D003110:Colonic Neoplasms / Q000378:metabolism; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000378:metabolism; D053843:DNA Mismatch Repair / Q000235:genetics / Q000502:physiology*; D045643:DNA Repair Enzymes / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D019281:Dimerization; D005982:Glutathione Transferase / Q000737:chemistry; D006801:Humans; D008297:Male; D008540:Meiosis / Q000502:physiology*; D000070956:MutL Proteins; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D051135:Rad51 Recombinase / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013737:Testis / Q000378:metabolism*
D002352:Carrier Proteins; C403623:MLH3 protein, human; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D000070956:MutL Proteins; D045643:DNA Repair Enzymes