PUBLICATION
Multisystem analyses of two Cockayne syndrome associated proteins CSA and CSB reveal shared and unique functions
- Authors
- Wu, Z., Zhu, X., Yu, Q., Xu, Y., Wang, Y.
- ID
- ZDB-PUB-190924-17
- Date
- 2019
- Source
- DNA repair 83: 102696 (Journal)
- Registered Authors
- Keywords
- CSA, CSB, Cockyane syndrome, Neurodegeneration, Transcription dysregulation
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Cockayne Syndrome/genetics*
- DNA Helicases/genetics
- DNA Helicases/metabolism*
- DNA Repair
- DNA Repair Enzymes/genetics
- DNA Repair Enzymes/metabolism*
- Humans
- Neurites/metabolism
- Poly-ADP-Ribose Binding Proteins/genetics
- Poly-ADP-Ribose Binding Proteins/metabolism*
- Transcription Factors/genetics
- Transcription Factors/metabolism*
- Zebrafish
- PubMed
- 31546172 Full text @ DNA Repair (Amst).
Citation
Wu, Z., Zhu, X., Yu, Q., Xu, Y., Wang, Y. (2019) Multisystem analyses of two Cockayne syndrome associated proteins CSA and CSB reveal shared and unique functions. DNA repair. 83:102696.
Abstract
Mutations in the CSA and CSB genes are causative of Cockayne syndrome neurological disorder. Since the identification of indispensable functions of these two proteins in transcription-coupled repair and restoring RNA synthesis following DNA damage, the paradoxical less severe clinical symptoms reported in some CS-A patients have been puzzling. In this study we compared the effects of a CSA or a CSB defect at the levels of the cell and the intact organism. We showed that CSA-deficient zebrafish embryos exhibited modest hypersensitive to UV damage than CSB depletion. We found that loss of CSA can effectively release aggregation of mutant crystallin proteins in vitro. We described the opposite effect of CSA and CSB on neuritogenesis and elucidated the differentiated gene expression pathways regulated by these two proteins. Our data demonstrate convergent and divergent roles for CSA and CSB in DNA repair and transcription regulation and provide potential explanations for the observed differences between CS-A and CS-B patients.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping