Abstract
DNA double-strand breaks (DSBs) are particularly hazardous lesions as their inappropriate repair can result in chromosome rearrangements, an important driving force of tumorigenesis. DSBs can be repaired by end joining mechanisms or by homologous recombination (HR). HR requires the action of several nucleases that preferentially remove the 5′-terminated strands at both DSB ends in a process called DNA end resection. The same nucleases are also involved in the processing of replication fork structures. Much of our understanding of these pathways has come from studies in the model organism Saccharomyces cerevisiae. Here, we review the current knowledge of the mechanism of resection at DNA DSBs and replication forks.
Highlights
DNA double-strand breaks (DSBs) are highly cytotoxic forms of DNA damage because their incorrect repair or failure to repair causes chromosome loss and rearrangements that can lead to cell death or transformation (Liu et al, 2012)
Loss of the WRN exonuclease activity enhances degradation at nascent DNA strands by EXO1 and MRE11 (Su et al, 2014; Iannascoli et al, 2015), whereas cells depleted of the biorientation defect 1-like (BOD1L) protein exhibit a DNA2-dependent degradation of stalled/damaged replication forks (Higgs et al, 2015)
Defects in homologous recombination (HR) and DNA replication underlie a significant proportion of the genomic instability observed in cancer cells
Summary
DNA double-strand breaks (DSBs) are highly cytotoxic forms of DNA damage because their incorrect repair or failure to repair causes chromosome loss and rearrangements that can lead to cell death or transformation (Liu et al, 2012). We will focus on the work done in S. cerevisiae to understand the resection mechanism at DNA DSBs and replication forks and its regulation by Tel1/ATM and Mec1/ATR checkpoint kinases.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
