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

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.

• Authors: Vesna Rapić-Otrin, Mary P McLenigan, Dawn C Bisi, Martin Gonzalez, Arthur S Levine
• Journal: Nucleic acids research (Nucleic Acids Res) Vol. 30 Issue 11 Pg. 2588-98 (Jun 01 2002) ISSN: 1362-4962 [Electronic] England
• PMID: 12034848 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 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

Topics

• 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