A novel interaction between human DNA polymerase eta and MutLalpha.
Human DNA polymerase eta (Poleta) is the gene product underlying xeroderma pigmentosum variant, and plays principal roles in translesion DNA synthesis. Here, we identified human MLH1, an essential component of mismatch repair (MMR), as a Poleta-interacting protein. The middle area residues, which include the little finger domain, of Poleta are important for the interaction with MLH1. Poleta also interacts with the MLH1/PMS2 heterodimer (MutLalpha). Co-immunoprecipitation analyses revealed that MutLalpha, and also MSH2 and MSH6, components of the MutSalpha heterodimer, form complexes with Poleta in human cells. Although MutSalpha had been reported to interact with C-terminal residues of Poleta, MutLalpha and MutSalpha co-precipitated with C-terminally truncated Poleta, suggesting that MutSalpha can interact with Poleta through MutLalpha. MMR proteins were more abundant in the Poleta complex on the chromatin of S phase-synchronized cells than of asynchronous cells, suggesting that the interaction between Poleta and MLH1 is involved in DNA replication.
Kanao
Rie
R
Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
Hanaoka
Fumio
F
Masutani
Chikahide
C
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D020798:Two-Hybrid System Techniques; D000099270:Y-Family DNA Polymerases
D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases; D002843:Chromatin; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D009687:Nuclear Proteins; C501486:MLH1 protein, human; C500929:MutLalpha protein, human; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases; C094934:PMS2 protein, human