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Ubiquitin and TFIIH-stimulated DDB2 dissociation drives DNA damage handover in nucleotide excision repair
- Source :
- Nature Communications, Vol 11, Iss 1, Pp 1-14 (2020), Nature Communications, Nature Communications, 11(1):4868. Nature Publishing Group
- Publication Year :
- 2020
- Publisher :
- Nature Portfolio, 2020.
-
Abstract
- DNA damage sensors DDB2 and XPC initiate global genome nucleotide excision repair (NER) to protect DNA from mutagenesis caused by helix-distorting lesions. XPC recognizes helical distortions by binding to unpaired ssDNA opposite DNA lesions. DDB2 binds to UV-induced lesions directly and facilitates efficient recognition by XPC. We show that not only lesion-binding but also timely DDB2 dissociation is required for DNA damage handover to XPC and swift progression of the multistep repair reaction. DNA-binding-induced DDB2 ubiquitylation and ensuing degradation regulate its homeostasis to prevent excessive lesion (re)binding. Additionally, damage handover from DDB2 to XPC coincides with the arrival of the TFIIH complex, which further promotes DDB2 dissociation and formation of a stable XPC-TFIIH damage verification complex. Our results reveal a reciprocal coordination between DNA damage recognition and verification within NER and illustrate that timely repair factor dissociation is vital for correct spatiotemporal control of a multistep repair process.<br />DNA damage sensors DDB2 and XPC are fundamental factors to initiate global genome nucleotide excision repair and protect DNA from mutagenesis. Here the authors reveal that ubiquitin and TFIIH-stimulated DDB2 dissociation promotes DNA damage handover to XPC in nucleotide excision repair.
- Subjects :
- 0301 basic medicine
Genomic instability
DNA Repair
DNA damage
DNA repair
Science
General Physics and Astronomy
General Biochemistry, Genetics and Molecular Biology
Article
Lesion
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Ubiquitin
medicine
Humans
lcsh:Science
Cell Nucleus
Multidisciplinary
Global genome nucleotide-excision repair
biology
Ubiquitination
General Chemistry
Cell biology
DNA-Binding Proteins
Nucleotide excision repair
030104 developmental biology
chemistry
Transcription factor II H
biology.protein
lcsh:Q
medicine.symptom
Transcription Factor TFIIH
030217 neurology & neurosurgery
DNA
DNA Damage
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....7af01a3689cd4ddf47e112ea7ae83b16