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Free keywords:
*DNA Breaks, Double-Stranded
DNA Repair/genetics/*physiology
DNA-Binding Proteins/metabolism
Fanconi Anemia Complementation Group Proteins/*metabolism
Genes, cdc/*physiology
Proteasome Endopeptidase Complex/metabolism
Signal Transduction/genetics/*physiology
Ubiquitin/*metabolism
Ubiquitin-Protein Ligases/*metabolism
Abstract:
Protein ubiquitylation has emerged as an important regulatory mechanism that impacts almost every aspect of the DNA damage response. In this review, we discuss how DNA repair and checkpoint pathways utilize the diversity offered by the ubiquitin conjugation system to modulate the response to genotoxic lesions in space and time. In particular, we will highlight recent work done on the regulation of DNA double-strand breaks signalling and repair by the RNF8/RNF168 E3 ubiquitin ligases, the Fanconi anemia pathway and the role of protein degradation in the enforcement and termination of checkpoint signalling. We also discuss the various functions of deubiquitylating enzymes in these processes along with potential avenues for exploiting the ubiquitin conjugation/deconjugation system for therapeutic purposes.
