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PMID: 12034848 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation.

Nucleic acids research ·Vol. 30 ·No. 11 ·2002-06-01 ·Pages 2588-98

Rapić-Otrin V, McLenigan MP, Bisi DC, Gonzalez M, Levine AS

Abstract

The UV-damaged DNA binding protein complex (UV-DDB) is implicated in global genomic nucleotide excision repair (NER) in mammalian cells. The complex consists of a heterodimer of p127 and p48. UV-DDB is defective in one complementation group (XP-E) of the heritable, skin cancer-prone disorder xeroderma pigmentosum. Upon UV irradiation of primate cells, UV-DDB associates tightly with chromatin, concomitant with the loss of extractable binding activity. We report here that an early event after UV, but not ionizing, radiation is the transient dose-dependent degradation of the small subunit, p48. Treatment of human cells with the proteasomal inhibitor NIP-L3VS blocks this UV-induced degradation of p48. In XP-E cell lines with impaired UV-DDB binding, p48 is resistant to degradation. UV-mediated degradation of p48 occurs independently of the expression of p53 and the cell's proficiency for NER, but recovery of p48 levels at later times (12 h and thereafter) is dependent upon the capacity of the cell to repair non-transcribed DNA. In addition, we find that the p127 subunit of UV-DDB binds in vivo to p300, a histone acetyltransferase. The data support a functional connection between UV-DDB binding activity, proteasomal degradation of p48 and chromatin remodeling during early steps of NER.

MeSH Terms
Acetyltransferases/metabolism Animals Cell Cycle Proteins/metabolism Cell Line Chlorocebus aethiops Chromatin/genetics,metabolism,radiation effects Cysteine Endopeptidases/metabolism DNA Damage/radiation effects DNA Repair DNA-Binding Proteins/chemistry,genetics,metabolism Dose-Response Relationship, Radiation Enzyme Inhibitors/pharmacology Histone Acetyltransferases Humans Molecular Weight Multienzyme Complexes/antagonists & inhibitors,metabolism Mutation/genetics Precipitin Tests Proteasome Endopeptidase Complex Protein Binding/radiation effects Protein Processing, Post-Translational/drug effects,radiation effects Protein Subunits RNA, Messenger/genetics,metabolism Radiation, Ionizing Transcription Factors Transcription, Genetic Tumor Suppressor Protein p53/metabolism Ultraviolet Rays p300-CBP Transcription Factors
Chemicals
Cell Cycle Proteins Chromatin DDB1 protein, human DDB2 protein, human DNA-Binding Proteins Enzyme Inhibitors Multienzyme Complexes Protein Subunits RNA, Messenger Transcription Factors Tumor Suppressor Protein p53 Acetyltransferases Histone Acetyltransferases p300-CBP Transcription Factors p300-CBP-associated factor Cysteine Endopeptidases Proteasome Endopeptidase Complex
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Rapić-Otrin Vesna
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, E1240 BST, Pittsburgh, PA 15261, USA.
McLenigan Mary P
Bisi Dawn C
Gonzalez Martin
Levine Arthur S
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/30.11.2588
Published
2002-06-01
Pages
2588-98
Language
English
Region
England
NLM ID
0411011
PMCID
PMC117178
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/30.11.2588 PMC Full Text View journal details
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