Ubiquitylation-independent degradation of Xeroderma pigmentosum group C protein is required for efficient nucleotide excision repair
Open Access
- 9 August 2007
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 35 (16), 5338-5350
- https://doi.org/10.1093/nar/gkm550
Abstract
The Xeroderma Pigmentosum group C (XPC) protein is indispensable to global genomic repair (GGR), a subpathway of nucleotide excision repair (NER), and plays an important role in the initial damage recognition. XPC can be modified by both ubiquitin and SUMO in response to UV irradiation of cells. Here, we show that XPC undergoes degradation upon UV irradiation, and this is independent of protein ubiquitylation. The subunits of DDB-Cul4A E3 ligase differentially regulate UV-induced XPC degradation, e.g DDB2 is required and promotes, whereas DDB1 and Cul4A protect the protein degradation. Mutation of XPC K655 to alanine abolishes both UV-induced XPC modification and degradation. XPC degradation is necessary for recruiting XPG and efficient NER. The overall results provide crucial insights regarding the fate and role of XPC protein in the initiation of excision repair.Keywords
This publication has 55 references indexed in Scilit:
- Distinct functions of the ubiquitin–proteasome pathway influence nucleotide excision repairThe EMBO Journal, 2006
- Function and regulation of cullin–RING ubiquitin ligasesNature Reviews Molecular Cell Biology, 2005
- In Vivo Recruitment of XPC to UV-induced Cyclobutane Pyrimidine Dimers by the DDB2 Gene ProductPublished by Elsevier BV ,2003
- The carboxy-terminal domain of the XPC protein plays a crucial role in nucleotide excision repair through interactions with transcription factor IIHDNA Repair, 2002
- Centrosome Protein Centrin 2/Caltractin 1 Is Part of the Xeroderma Pigmentosum Group C Complex That Initiates Global Genome Nucleotide Excision RepairPublished by Elsevier BV ,2001
- Protein modification by SUMOTrends in Biochemical Sciences, 2001
- Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sitesJournal of Molecular Biology, 2000
- Solution-state structure of a DNA dodecamer duplex containing a Cis-Syn thymine cyclobutane dimer, the major UV photoproduct of DNAJournal of Molecular Biology, 1998
- Reconstitution of Human DNA Repair Excision Nuclease in a Highly Defined SystemPublished by Elsevier BV ,1995
- Expression cloning of a human DNA repair gene involved in xeroderma pigmentosum group CNature, 1992