DNA mismatch repair and the DNA damage response to ionizing radiation: Making sense of apparently conflicting data

• Published in: Cancer treatment reviews Vol. 36; no. 7; pp. 518 - 527
• Main Authors: Martin, Lynn M., Marples, Brian, Coffey, Mary, Lawler, Mark, Lynch, Thomas H., Hollywood, Donal, Marignol, Laure
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.11.2010
• Subjects: Animals; Apoptosis; Cell cycle arrest; Cell Division - radiation effects; DNA - radiation effects; DNA Damage; DNA Mismatch Repair; G2 Phase - radiation effects; G2/M; Hematology, Oncology and Palliative Medicine; Humans; Hypersensitivity; Ionizing radiation; Low dose; MLH1; MSH2; RAD51; Radiation Tolerance; Recombination, Genetic; Review; Ionizing radiation; RAD51; MSH2; Low dose; Hypersensitivity; G2/M; Cell cycle arrest; Review; MLH1; DNA mismatch repair
• ISSN: 0305-7372; 1532-1967; 1532-1967
• DOI: 10.1016/j.ctrv.2010.03.008

The DNA mismatch repair (MMR) pathway detects and repairs DNA replication errors. While DNA MMR-proficiency is known to play a key role in the sensitivity to a number of DNA damaging agents, its role in the cytotoxicity of ionizing radiation (IR) is less well characterized. Available literature to date is conflicting regarding the influence of MMR status on radiosensitivity, and this has arisen as a subject of controversy in the field. The aim of this paper is to provide the first comprehensive overview of the experimental data linking MMR proteins and the DNA damage response to IR. A PubMed search was conducted using the key words “DNA mismatch repair” and “ionizing radiation”. Relevant articles and their references were reviewed for their association between DNA MMR and IR. Recent data suggest that radiation dose and the type of DNA damage induced may dictate the involvement of the MMR system in the cellular response to IR. In particular, the literature supports a role for the MMR system in DNA damage recognition, cell cycle arrest, DNA repair and apoptosis. In this review we discuss our current understanding of the impact of MMR status on the cellular response to radiation in mammalian cells gained from past and present studies and attempt to provide an explanation for how MMR may determine the response to radiation.