EXO1 resection at G-quadruplex structures facilitates resolution and replication. Issue 9 (31st March 2020)

• Record Type: Journal Article
• Authors: Stroik, Susanna; Kurtz, Kevin; Lin, Kevin; Karachenets, Sergey; Myers, Chad L; Bielinsky, Anja-Katrin; Hendrickson, Eric A
• Is Part Of: Nucleic acids research. Volume 48:Issue 9(2020)
• Page Start: 4960
• Page End: 4975
• Publication Date: 2020-03-31
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkaa199
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: G-quadruplexes represent unique roadblocks to DNA replication, which tends to stall at these secondary structures. Although G-quadruplexes can be found throughout the genome, telomeres, due to their G-richness, are particularly predisposed to forming these structures and thus represent difficult-to-replicate regions. Here, we demonstrate that exonuclease 1 (EXO1) plays a key role in the resolution of, and replication through, telomeric G-quadruplexes. When replication forks encounter G-quadruplexes, EXO1 resects the nascent DNA proximal to these structures to facilitate fork progression and faithful replication. In the absence of EXO1, forks accumulate at stabilized G-quadruplexes and ultimately collapse. These collapsed forks are preferentially repaired via error-prone end joining as depletion of EXO1 diverts repair away from error-free homology-dependent repair. Such aberrant repair leads to increased genomic instability, which is exacerbated at chromosome termini in the form of dysfunction and telomere loss.