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Trends Biochem Sci. 2012 Feb;37(2):66-73. doi: 10.1016/j.tibs.2011.10.004. Epub 2011 Nov 16.

SCF ubiquitin ligases in the maintenance of genome stability.

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Department of Radiation Oncology, New York University School of Medicine, 522 First Avenue, Smilow Research Building 1107, New York, NY 10016, USA.


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.

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