1. EXO1 resection at G-quadruplex structures facilitates resolution and replication.
- Author
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Stroik S, Kurtz K, Lin K, Karachenets S, Myers CL, Bielinsky AK, and Hendrickson EA
- Subjects
- Aminoquinolines pharmacology, Cell Line, DNA End-Joining Repair, DNA Repair, DNA Repair Enzymes genetics, DNA Repair Enzymes metabolism, Exodeoxyribonucleases genetics, Exodeoxyribonucleases metabolism, Gene Knockout Techniques, HeLa Cells, Humans, Neoplasms metabolism, Neoplasms mortality, Picolinic Acids pharmacology, Prognosis, DNA Repair Enzymes physiology, DNA Replication, Exodeoxyribonucleases physiology, G-Quadruplexes drug effects, Telomere chemistry
- 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., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2020
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