Rad9 plays an important role in DNA mismatch repair through physical interaction with MLH1.
Rad9 is conserved from yeast to humans and plays roles in DNA repair (homologous recombination repair, and base-pair excision repair) and cell cycle checkpoint controls. It has not previously been reported whether Rad9 is involved in DNA mismatch repair (MMR). In this study, we have demonstrated that both human and mouse Rad9 interacts physically with the MMR protein MLH1. Disruption of the interaction by a single-point mutation in Rad9 leads to significantly reduced MMR activity. This disruption does not affect S/M checkpoint control and the first round of G(2)/M checkpoint control, nor does it alter cell sensitivity to UV light, gamma rays or hydroxyurea. Our data indicate that Rad9 is an important factor in MMR and carries out its MMR function specifically through interaction with MLH1.
National Laboratory of Biomacromolecules, Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Wei
W
He
Yun
Y
Zhao
Chunbo
C
Zhang
Lili
L
An
Zhishang
Z
Hu
Yuheng
Y
Liu
Lu
L
Han
Lijun
L
Bi
Zhensheng
Z
Xie
Peng
P
Xue
Fuquan
F
Yang
Haiying
H
Hang
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D019943:Amino Acid Substitution; D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D004249:DNA Damage; D053843:DNA Mismatch Repair; D005092:Exonucleases / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D012694:Serine / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C462949:HUS1B protein, human; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C069930:rad9 protein; D012694:Serine; D005092:Exonucleases; C113574:Rad1 protein, human; D000070957:MutL Protein Homolog 1