The proper DNA damage response (DDR) and repair are the central molecular mechanisms for the maintenance of cellular homeostasis and genomic integrity. The abnormality in this process is frequently observed in human
cancers, and is an important contributing factor to
cancer development. FBXW7 is an
F-box protein serving as the substrate recognition component of SCF (SKP1-CUL1-F-box protein)
E3 ubiquitin ligase. By selectively targeting many
oncoproteins for
proteasome-mediated degradation, FBXW7 acts as a typical
tumor suppressor. Recent studies have demonstrated that FBXW7 also plays critical roles in the process of DDR and repair. In this review, we first briefly introduce the processes of
protein ubiquitylation by SCFFBXW7 and DDR/repair, then provide an overview of the molecular characteristics of FBXW7. We next discuss how FBXW7 regulates the process of DDR and repair, and its translational implication. Finally, we propose few future perspectives to further elucidate the role of FBXW7 in regulation of a variety of biological processes and
tumorigenesis, and to design a number of approaches for FBXW7 reactivation in a subset of human
cancers for potential anticancer
therapy.