EXO1 resection at G-quadruplex structures facilitates resolution and replication

Susanna Stroik, Kevin Kurtz, Kevin Lin, Sergey Karachenets, Chad L. Myers, Anja Katrin Bielinsky, Eric A. Hendrickson

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4960-4975
Number of pages16
JournalNucleic acids research
Volume48
Issue number9
DOIs
StatePublished - May 21 2020

Bibliographical note

Publisher Copyright:
© 2020 The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

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