Cancer from the outside, aging from the inside: Mouse models to study the consequences of defective nucleotide excision repair

Jan De Boer, Jan H.J. Hoeijmakers

Research output: Contribution to journalArticleAcademicpeer-review

72 Citations (Scopus)

Abstract

In recent years, mouse models have been generated to study the syndromes associated with a defect in nucleotide excision repair (NER). Thus, via conventional knockout gene targeting or by mimicking patient-specific alleles, mouse models for xeroderma pigmentosum (XP), Cockayne syndrome (CS) and photosensitive trichothiodystrophy (TTD) have been obtained. The generation of this series of mouse mutants allows in vivo investigation of some intriguing questions that have puzzled the field, such as the paradoxical absence of cancer development in TTD and CS despite their NER deficiencies, and the role of the ERCC1 gene in mitotic recombination and cross-link repair. Other interesting issues include the pathophysiology of the non-NER related clinical symptoms in TTD and CS patients and the proposed involvement of NER and transcription in the process of aging. This review will focus on data obtained thus far and discuss further utilization of the mouse mutants for unraveling some of the fascinating and medically relevant aspects associated with defects in NER and related processes.

Original languageEnglish
Pages (from-to)127-137
Number of pages11
JournalBiochimie
Volume81
Issue number1-2
DOIs
Publication statusPublished - Jan 1999
Externally publishedYes

Keywords

  • Aging
  • Genetic instability
  • Human repair syndromes
  • Mouse model

Fingerprint

Dive into the research topics of 'Cancer from the outside, aging from the inside: Mouse models to study the consequences of defective nucleotide excision repair'. Together they form a unique fingerprint.

Cite this