Divide and conquer: nucleotide excision repair battles cancer and ageing.

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.

journal_name

Curr Opin Cell Biol

authors

Mitchell JR,Hoeijmakers JH,Niedernhofer LJ

doi

10.1016/s0955-0674(03)00018-8

subject

Has Abstract

pub_date

2003-04-01 00:00:00

pages

232-40

issue

2

eissn

0955-0674

issn

1879-0410

pii

S0955067403000188

journal_volume

15

pub_type

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