The role of mismatch repair in DNA damage-induced apoptosis

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

DNA mismatch repair plays a critical role in maintaining genomic integrity. Defects in human mismatch repair are the primary cause of certain types of cancer, including hereditary nonpolyposis colorectal cancer. In the past, the ability of mismatch repair proteins to correct DMA mismatches that occur during DNA replication, repair, and recombination was considered the primary mechanism by which it contributes to genomic stability. However, increasing evidence supports the idea that the mismatch repair system also contributes to genome stability by stimulating DNA damage-induced apoptosis as part of the cyloloxic response to physical and chemical agents. MutS/MutL homologues mediate the process of apoptosis by binding to DNA adducts and either provoking futile repair events or blocking steps in DNA metabolism (i.e., DNA replication and/or repair). This damage recognition step by mismatch repair (MMR) proteins stimulates a signaling cascade for apoptosis, resulting in activation of protein kinase(s) that phosphorylate p53 and/or the related protein p73. Activated p53 and p73 in turn transmit a signal to the apoptotic machinery to execute cell death. The goal of this commentary is to discuss the molecular mechanism(s) by which mismatch repair proteins stimulate apoptosis.

Original languageEnglish (US)
Pages (from-to)393-400
Number of pages8
JournalOncology Research
Volume11
Issue number9
StatePublished - Dec 1 1999

Fingerprint

DNA Mismatch Repair
DNA Damage
Apoptosis
Genomic Instability
DNA Replication
DNA Repair
Hereditary Nonpolyposis Colorectal Neoplasms
Proteins
DNA Adducts
Protein Kinases
Genetic Recombination
Cell Death
DNA
Neoplasms

Keywords

  • Apoptosis
  • Cancer
  • Genomic instability
  • Mismatch repair

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The role of mismatch repair in DNA damage-induced apoptosis. / Li, Guo Min.

In: Oncology Research, Vol. 11, No. 9, 01.12.1999, p. 393-400.

Research output: Contribution to journalArticle

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