A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein
| Autor: | Jessica M. Y. Ng, Jan H.J. Hoeijmakers, Steven Bergink, Gijsbertus T. J. van der Horst, Kaoru Sugasawa, Wim Vermeulen, Harry Vrieling |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Proteasome Endopeptidase Complex Xeroderma pigmentosum Hot Temperature DNA Repair Transcription Genetic DNA damage DNA repair Ultraviolet Rays Recombinant Fusion Proteins Saccharomyces cerevisiae Acetoxyacetylaminofluorene Transfection Cell Line Mice Ubiquitin Multienzyme Complexes Genetics medicine Animals Humans Gene Mice Knockout Global genome nucleotide-excision repair biology medicine.disease biology.organism_classification Molecular biology Research Papers DNA-Binding Proteins Mice Inbred C57BL Cysteine Endopeptidases DNA Repair Enzymes Gene Targeting biology.protein Female Developmental Biology Nucleotide excision repair DNA Damage |
| Zdroj: | Genesdevelopment. 17(13) |
| ISSN: | 0890-9369 |
| Popis: | 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 thatmHR23AandmHR23Bhave 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 ofmHR23A/Bdouble-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. |
| Databáze: | OpenAIRE |
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