Contributions of DNA interstrand cross-links to aging of cells and organisms.

Abstract:

:Impaired DNA damage repair, especially deficient transcription-coupled nucleotide excision repair, leads to segmental progeroid syndromes in human patients as well as in rodent models. Furthermore, DNA double-strand break signalling has been pinpointed as a key inducer of cellular senescence. Several recent findings suggest that another DNA repair pathway, interstrand cross-link (ICL) repair, might also contribute to cell and organism aging. Therefore, we summarize and discuss here that (i) systemic administration of anti-cancer chemotherapeutics, in many cases DNA cross-linking drugs, induces premature progeroid frailty in long-term survivors; (ii) that ICL-inducing 8-methoxy-psoralen/UVA phototherapy leads to signs of premature skin aging as prominent long-term side effect and (iii) that mutated factors involved in ICL repair like ERCC1/XPF, the Fanconi anaemia proteins, WRN and SNEV lead to reduced replicative life span in vitro and segmental progeroid syndromes in vivo. However, since ICL-inducing drugs cause damage different from ICL and since all currently known ICL repair factors work in more than one pathway, further work will be needed to dissect the actual contribution of ICL damage to aging.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Grillari J,Katinger H,Voglauer R

doi

10.1093/nar/gkm1065

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

7566-76

issue

22

eissn

0305-1048

issn

1362-4962

pii

gkm1065

journal_volume

35

pub_type

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