Divide and conquer: Nucleotide excision repair battles cancer and ageing

James R. Mitchell, Jan H.J. Hoeijmakers, Laura J. Niedernhofer

Research output: Contribution to journalReview articlepeer-review

122 Scopus citations

Abstract

Protection from cancer and ensured longevity are tightly linked in mammals. One of the fundamental mechanisms contributing to both is the cellular response to DNA damage. The appropriate response is an initial attempt at repair, but if the damage is too extensive or compromises DNA metabolism, a signalling cascade triggers cellular senescence or death. Evidence in mice and humans suggests a division of tasks amongst DNA repair pathways: transcription-coupled repair and interstrand crosslink repair of cytotoxic lesions are predominantly responsible for longevity assurance, whereas excision repair of mutagenic lesions provides protection against cancer. Similarly, the signalling component of the DNA-damage response might contribute unequally to organismal outcomes depending on its set point: an inadequate response to DNA damage sanctions carcinogenesis but might limit local ageing, whereas overzealous signalling provides cancer protection but accelerates ageing.

Original languageEnglish (US)
Pages (from-to)232-240
Number of pages9
JournalCurrent Opinion in Cell Biology
Volume15
Issue number2
DOIs
StatePublished - Apr 2003
Externally publishedYes

Bibliographical note

Funding Information:
JR Mitchell is supported in part by DRG1677 from the Damon Runyon Cancer Research Foundation. LJ Niedernhofer was supported by postdoctoral fellowship number PF-99-142 from the American Cancer Society.

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