Premium
Role of DNA mismatch repair in apoptotic responses to therapeutic agents
Author(s) -
Meyers Mark,
Hwang Arlene,
Wagner Mark W.,
Boothman David A.
Publication year - 2004
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.20056
Subject(s) - dna repair , apoptosis , dna damage , dna , biology , genetics , computational biology
Deficiencies in DNA mismatch repair (MMR) have been found in both hereditary cancer (i.e., hereditary nonpolyposis colorectal cancer) and sporadic cancers of various tissues. In addition to its primary roles in the correction of DNA replication errors and suppression of recombination, research in the last 10 years has shown that MMR is involved in many other processes, such as interaction with other DNA repair pathways, cell cycle checkpoint regulation, and apoptosis. Indeed, a cell's MMR status can influence its response to a wide variety of chemotherapeutic agents, such as temozolomide (and many other methylating agents), 6‐thioguanine, cisplatin, ionizing radiation, etoposide, and 5‐fluorouracil. For this reason, identification of a tumor's MMR deficiency (as indicated by the presence of microsatellite instability) is being utilized more and more as a prognostic indicator in the clinic. Here, we describe the basic mechanisms of MMR and apoptosis and investigate the literature examining the influence of MMR status on the apoptotic response following treatment with various therapeutic agents. Furthermore, using isogenic MMR‐deficient (HCT116) and MMR‐proficient (HCT116 3‐6) cells, we demonstrate that there is no enhanced apoptosis in MMR‐proficient cells following treatment with 5‐fluoro‐2′‐deoxyuridine. In fact, apoptosis accounts for only a small portion of the induced cell death response. Environ. Mol. Mutagen. 44:249–264, 2004. © 2004 Wiley‐Liss, Inc.