The ubiquitous role of ubiquitin in the DNA damage response.
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.
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, M5G 1X5, ON, Canada.
Abdallah
A
Al-Hakim
Cristina
C
Escribano-Diaz
Marie-Claude
MC
Landry
Lara
L
O'Donnell
Stephanie
S
Panier
Rachel K
RK
Szilard
Daniel
D
Durocher
D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D051856:Fanconi Anemia Complementation Group Proteins / Q000378:metabolism*; D018816:Genes, cdc / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051856:Fanconi Anemia Complementation Group Proteins; C486521:RNF8 protein, human; D025801:Ubiquitin; C535210:RNF168 protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex