Abstract
DNA double-strand breaks (DSBs) are one of the most detrimental lesions, as their incorrect or incomplete repair can lead to genomic instability, a hallmark of cancer. Cells have evolved two major competing DSB repair mechanisms: Homologous recombination (HR) and non-homologous end joining (NHEJ). HR is initiated by DNA-end resection, an evolutionarily conserved process that generates stretches of single-stranded DNA tails that are no longer substrates for religation by the NHEJ machinery. Ubiquitylation and sumoylation, the covalent attachment of ubiquitin and SUMO moieties to target proteins, play multifaceted roles in DNA damage signaling and have been shown to regulate HR and NHEJ, thus ensuring appropriate DSB repair. Here, we give a comprehensive overview about the current knowledge of how ubiquitylation and sumoylation control DSB repair by modulating the DNA-end resection machinery.
Highlights
The capacity of our cells to detect and repair damaged DNA is key to prevent genomic instability and the development of cancer (Jackson and Bartek, 2009; Ciccia and Elledge, 2010)
DNA double-strand breaks (DSBs) are hazardous lesions as their inappropriate repair can result in chromosomal translocations, an important driving force of tumorigenesis (Hanahan and Weinberg, 2011; Forment et al, 2012; Bunting and Nussenzweig, 2013; Rodgers and McVey, 2016)
homologous recombination (HR) is initiated by DNA-end resection, an evolutionarily conserved mechanism that generates long stretches of 3 single-stranded DNA overhangs by nucleolytic degradation of the 5 terminated strand of the DSB (Symington, 2014; Cejka, 2015; Daley et al, 2015)
Summary
The capacity of our cells to detect and repair damaged DNA is key to prevent genomic instability and the development of cancer (Jackson and Bartek, 2009; Ciccia and Elledge, 2010). The anaphase-promoting complex/cyclosome-Cdh (APC/CCdh1) E3 ubiquitin ligase was shown to control cell cycle-dependent repair of DSBs by targeting CtIP for proteasomal degradation after mitotic exit as well as after DNA damage in G2 phase (Figure 1B) (Lafranchi et al, 2014). Such a mechanism would counteract resection of DSBs and allow efficient C-NHEJ in G1 cells, where the intact sister chromatid is not available for HR.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
