title: Mismatch repair proteins as sensors of alkylation DNA damage.
abstract: 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.
authors.affiliation: 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
authors.forename: Jean Y J
authors.initials: JY
authors.lastname: Wang
authors.forename: Winfried
authors.initials: W
authors.lastname: Edelmann
mesh_terms: 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
chemical_list: 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