Mismatch repair proteins as sensors of alkylation DNA damage.
The DNA mismatch repair (MMR) system maintains genome integrity by correcting replication errors. MMR also stimulates checkpoint and cell death responses to DNA damage suggested by the resistance of MMR-defective tumor cells to several chemotherapeutic agents. MMR-dependent cytotoxic response may result from futile repair; however, MMR-mediated apoptosis has been genetically separated from its repair function. In a recent issue of Molecular Cell, Yoshioka and coworkers show that MMR complexes (MutSalpha and MutLalpha) are required for the recruitment of ATR-ATRIP to sites of alkylation damage, demonstrating that MMR complexes can function as sensors in DNA damage signal transduction.
Wang
Jean Y J
JY
Division of Hematology/Oncology, Department of Medicine and Moores Cancer Center, University of California, San Diego, School of Medicine, 3855 Health Sciences Drive, La Jolla, California 92093, USA. jywang@ucsd.edu
Edelmann
Winfried
W
D048868:Adaptor Proteins, Signal Transducing; D000478:Alkylation; D000818:Animals; D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins; D020137:Base Pair Mismatch; D018797:Cell Cycle Proteins / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D006801:Humans; D051719:MutS DNA Mismatch-Binding Protein / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction
C521194:ATRIP protein, human; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D005090:Exodeoxyribonucleases; C429526:three prime repair exonuclease 1; D051719:MutS DNA Mismatch-Binding Protein