DOI: 10.1101/gad.260003. A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein

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

10.1101/gad.260003

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

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 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.

Bibliography

Ng, J. M. Y., Vermeulen, W., van der Horst, G. T. J., Bergink, S., Sugasawa, K., Vrieling, H., & Hoeijmakers, J. H. J. (2003). A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein. Genes & Development, 17(13), 1630â1645.

Authors 7

Jessica M.Y. Ng (first)
Wim Vermeulen (additional)
Gijsbertus T.J. van der Horst (additional)
Steven Bergink (additional)
Kaoru Sugasawa (additional)
Harry Vrieling (additional)
Jan H.J. Hoeijmakers (additional)

References 54 Referenced 188

10.1073/pnas.202485699
10.4161/cbt.59
10.1074/jbc.M100855200
10.1038/87575
10.1083/jcb.133.6.1331
{'key': '2021111519023255000_17.13.1630.6', 'first-page': '677', 'volume': '1', 'year': '2001', 'journal-title': 'The metabolic and molecular bases of inherited disease'} / The metabolic and molecular bases of inherited disease (2001)
10.1128/MCB.22.13.4902-4913.2002
10.1093/embo-reports/kve203
10.1128/MCB.21.6.1997-2007.2001
Friedberg E.C. , Walker, G.C., and Siede, W. 1995. DNA repair and mutagenesis. ASM Press, Washington, DC.
10.1101/gad.869601
10.1101/gad.9.1.1
10.1038/35013197
10.1093/emboj/21.6.1456
10.1074/jbc.274.39.28019
10.1038/35077232
10.1016/S1097-2765(02)00709-8
10.1126/science.284.5416.958
10.1038/nrm731
10.1074/jbc.274.26.18785
10.1093/genetics/153.1.69 / Genetics (1999)
10.1006/bbrc.2000.2100
10.1093/nar/28.24.4839
10.1007/s00294-002-0332-9
10.1002/j.1460-2075.1994.tb06452.x / EMBO J. (1994)
10.1128/MCB.17.12.6915 / Mol. Cell. Biol. (1997)
10.1016/S0027-5107(00)00039-7
10.1074/jbc.M001064200
10.1128/MCB.22.4.1233-1245.2002
10.1038/35023547
{'key': '2021111519023255000_17.13.1630.31', 'first-page': '544', 'volume': '25', 'year': '2002', 'journal-title': 'Trends Biochem. Sci.'} / Trends Biochem. Sci. (2002)
10.1074/jbc.M200245200
10.1016/S1097-2765(01)80001-0
10.1038/35661
10.1007/BF00420608
10.1128/MCB.16.9.4852 / Mol. Cell. Biol. (1996)
10.1128/MCB.17.12.6924 / Mol. Cell. Biol. (1997)
10.1016/S1097-2765(00)80132-X
10.1101/gad.866301
10.1146/annurev.genet.34.1.479
10.1093/nar/24.13.2551
10.1006/geno.1996.0004
10.1093/nar/18.3.443
10.1016/0921-8777(95)00045-3
{'key': '2021111519023255000_17.13.1630.45', 'first-page': '191', 'volume': '54', 'year': '1994', 'journal-title': 'Am. J. Hum. Genet.'} / Am. J. Hum. Genet. (1994)
10.1016/S1097-2765(01)00281-7
{'key': '2021111519023255000_17.13.1630.47', 'first-page': '7757', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. (1993)
10.1016/S0027-5107(98)00035-9 / Mutat. Res. (1998)
10.1016/S0092-8674(00)81054-5
10.1038/ncb1001-939
Wood R.D. , Hanawalt, P.C., Mer, G., and Cooper, P.K. 2000. Nucleotide excision repair. In Biological responses to DNA damage, pp. 173–182. Cold Spring Harb. Symp. Quant. Biol. LXV. (10.1101/sqb.2000.65.173)
10.1126/science.1056154
10.1074/jbc.275.13.9870
{'key': '2021111519023255000_17.13.1630.54', 'first-page': '64', 'volume': '61', 'year': '2001', 'journal-title': 'Cancer Res.'} / Cancer Res. (2001)

Dates

Type	When
Created	22 years, 2 months ago (June 23, 2003, 8:32 p.m.)
Deposited	3 years, 9 months ago (Nov. 15, 2021, 10:14 p.m.)
Indexed	1 week, 2 days ago (Aug. 29, 2025, 6:20 a.m.)
Issued	22 years, 2 months ago (June 18, 2003)
Published	22 years, 2 months ago (June 18, 2003)
Published Online	22 years, 2 months ago (June 18, 2003)
Published Print	22 years, 2 months ago (July 1, 2003)

Funders 0

None

BibTeX

@article{Ng_2003, title={A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein}, volume={17}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.260003}, DOI={10.1101/gad.260003}, number={13}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Ng, Jessica M.Y. and Vermeulen, Wim and van der Horst, Gijsbertus T.J. and Bergink, Steven and Sugasawa, Kaoru and Vrieling, Harry and Hoeijmakers, Jan H.J.}, year={2003}, month=jun, pages={1630–1645} }

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