A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein

Jessica M.Y. Ng, Wim Vermeulen, Gijsbertus T.J. Van der Horst, Steven Bergink, Kaoru Sugasawa, Harry Vrieling, Jan H.J. Hoeijmakers

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

204 Citaten (Scopus)

Samenvatting

Primary DNA damage sensing in mammalian global genome nucleotide excision repair (GG-NER) is performed by the xeroderma pigmentosum group C (XPC)/HR23B protein complex. HR23B and HR23A are human homologs of the yeast ubiquitin-domain repair factor RAD23, the function of which is unknown. Knockout mice revealed that mHR23A and mHR23B have a fully redundant role in NER, and a partially redundant function in embryonic development. Inactivation of both genes causes embryonic lethality, but appeared still compatible with cellular viability. Analysis of mHR23A/B double-mutant cells showed that HR23 proteins function in NER by governing XPC stability via partial protection against proteasomal degradation. Interestingly, NER-type DNA damage further stabilizes XPC and thereby enhances repair. These findings resolve the primary function of RAD23 in repair and reveal a novel DNA-damage-dependent regulation mechanism of DNA repair in eukaryotes, which may be part of a more global damage-response circuitry.

Originele taal-2Engels
Pagina's (van-tot)1630-1645
Aantal pagina's16
TijdschriftGenes and Development
Volume17
Nummer van het tijdschrift13
DOI's
StatusGepubliceerd - 1 jul. 2003
Extern gepubliceerdJa

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