A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein
- Jessica M.Y. Ng1,
- Wim Vermeulen1,
- Gijsbertus T.J. van der Horst1,
- Steven Bergink1,
- Kaoru Sugasawa3,4,
- Harry Vrieling2, and
- Jan H.J. Hoeijmakers1,5
- 1MGC-Department of Cell Biology & Genetics, Centre for Biomedical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands 2 MGC-Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Center, 2333 AL Leiden, The Netherlands 3 Cellular Physiology Laboratory, RIKEN (The Institute of Physical and Chemical Research), and 4 Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Wako, Saitama 351-0198, Japan
Abstract
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.
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Footnotes
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Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.260003.
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Corresponding author.
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↵5 E-MAIL j.hoeijmakers{at}erasmusmc.nl; FAX 31-10-4089468.
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- Accepted April 30, 2003.
- Received January 14, 2003.
- Cold Spring Harbor Laboratory Press
