PUBLICATION
DNA damage during the G0/G1 phase triggers RNA-templated, Cockayne syndrome B-dependent homologous recombination
- Authors
- Wei, L., Nakajima, S., Böhm, S., Bernstein, K.A., Shen, Z., Tsang, M., Levine, A.S., Lan, L.
- ID
- ZDB-PUB-150624-6
- Date
- 2015
- Source
- Proceedings of the National Academy of Sciences of the United States of America 112(27): E3495-504 (Journal)
- Registered Authors
- Tsang, Michael
- Keywords
- CSB, DNA damage, RNA polymerase II, recombination, transcription
- MeSH Terms
-
- DNA Helicases/genetics*
- DNA Helicases/metabolism
- Cells, Cultured
- Replication Protein A/genetics
- Replication Protein A/metabolism
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism
- DNA Repair Enzymes/genetics*
- DNA Repair Enzymes/metabolism
- DNA Damage*
- Cell Cycle/genetics*
- Resting Phase, Cell Cycle/genetics
- Humans
- Rad51 Recombinase/genetics
- Rad51 Recombinase/metabolism
- Cockayne Syndrome/genetics
- Cockayne Syndrome/metabolism
- Cockayne Syndrome/pathology
- HeLa Cells
- RNA Interference
- Models, Genetic
- Antigens, Nuclear/genetics
- Antigens, Nuclear/metabolism
- Blotting, Western
- HEK293 Cells
- Cell Cycle Proteins/genetics
- Cell Cycle Proteins/metabolism
- Nuclear Proteins/genetics
- Nuclear Proteins/metabolism
- Microscopy, Confocal
- Homologous Recombination*
- DNA Repair
- Rad52 DNA Repair and Recombination Protein/genetics
- Rad52 DNA Repair and Recombination Protein/metabolism
- G1 Phase/genetics
- RNA/genetics*
- RNA/metabolism
- Transcription, Genetic
- Cell Line, Tumor
- PubMed
- 26100862 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Wei, L., Nakajima, S., Böhm, S., Bernstein, K.A., Shen, Z., Tsang, M., Levine, A.S., Lan, L. (2015) DNA damage during the G0/G1 phase triggers RNA-templated, Cockayne syndrome B-dependent homologous recombination. Proceedings of the National Academy of Sciences of the United States of America. 112(27):E3495-504.
Abstract
Damage repair mechanisms at transcriptionally active sites during the G0/G1 phase are largely unknown. To elucidate these mechanisms, we introduced genome site-specific oxidative DNA damage and determined the role of transcription in repair factor assembly. We find that KU and NBS1 are recruited to damage sites independent of transcription. However, assembly of RPA1, RAD51C, RAD51, and RAD52 at such sites is strictly governed by active transcription and requires both wild-type Cockayne syndrome protein B (CSB) function and the presence of RNA in the G0/G1 phase. We show that the ATPase activity of CSB is indispensable for loading and binding of the recombination factors. CSB counters radiation-induced DNA damage in both cells and zebrafish models. Taken together, our results have uncovered a novel, RNA-based recombination mechanism by which CSB protects genome stability from strand breaks at transcriptionally active sites and may provide insight into the clinical manifestations of Cockayne syndrome.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping