SCF ubiquitin ligases in the maintenance of genome stability

• Published in: Trends in biochemical sciences (Amsterdam. Regular ed.) Vol. 37; no. 2; pp. 66 - 73
• Main Authors: Silverman, Joshua S., Skaar, Jeffrey R., Pagano, Michele
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2012
• Subjects: aneuploidy; Animals; antineoplastic agents; cell cycle checkpoints; centrosomes; chromosome segregation; DDR; DNA Damage; DNA repair; eukaryotic cells; genome; Genomic Instability; genotoxicity; Humans; mutation; proteasome endopeptidase complex; proteins; SKP Cullin F-Box Protein Ligases - chemistry; SKP Cullin F-Box Protein Ligases - genetics; SKP Cullin F-Box Protein Ligases - metabolism; therapeutics; ubiquitin-protein ligase; Ubiquitination - genetics
• ISSN: 0968-0004; 1362-4326; 0968-0004
• DOI: 10.1016/j.tibs.2011.10.004

In response to genotoxic stress, eukaryotic cells activate the DNA damage response (DDR), a series of pathways that coordinate cell cycle arrest and DNA repair to prevent deleterious mutations. In addition, cells possess checkpoint mechanisms that prevent aneuploidy by regulating the number of centrosomes and spindle assembly. Among these mechanisms, ubiquitin-mediated degradation of key proteins has an important role in the regulation of the DDR, centrosome duplication and chromosome segregation. This review discusses the functions of a group of ubiquitin ligases, the SCF (SKP1-CUL1-F-box protein) family, in the maintenance of genome stability. Given that general proteasome inhibitors are currently used as anticancer agents, a better understanding of the ubiquitylation of specific targets by specific ubiquitin ligases may result in improved cancer therapeutics.