Moriwaki, Takahito et al. (2011) International Worm Meeting "The analysis of mismatch repair in C. elegans."

Zhang-Akiyama, Qiu-Mei, Moriwaki, Takahito, Kato, Yuichi, Ishikawa, Satoru, Hashiguti, Kazunari

[International Worm Meeting, 2011]

DNA mismatch repair (MMR) is an important genome caretaker system, and is highly conserved from bacteria to humans. MMR corrects base-base mismatches and small insertion / deletion mispairs generated during DNA replication, recombination and repair. In addition to correcting mismatches, MMR has various roles to maintain genomic stability. Recently, it was found that MMR works in DNA damage response (DDR). Because of generating mismatch in DNA replication, however, it is difficult to analysis the DDR function of MMR in whole-body level by using MMR defect mutants. Our purpose is to evaluate the contribution of MMR in whole-body level. C. elegans stop DNA replication after hatching. Hence we selected C. elegans to analyze this function. In C. elegans, the following four MMR enzymes have been identified; MSH2, MSH6, MLH1 and PMS2. From previous reports in other species, it is predicted that these enzymes form heterodimer, MutSa(MSH2-MSH6) and MutLa(MLH1-PMS2). We obtained mutants of each genes. In drug resistant tests, all mutants are resistant to MNNG. This result fits past report. But to MMS, some mutants are sensitive. This difference implies unknown dimers and pathways. We hypothesize MMR use some patterns of repair to response various damage.