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Homologous recombination repair intermediates promote efficient de novo telomere addition at DNA double-strand breaks
journal contribution
posted on 2023-06-09, 20:25 authored by Anoushka Dave, Chen-Chun Pai, Samuel C Durley, Lydia Hulme, Sovan Sarkar, Boon-Yu Wee, John Prudden, Helen Tinline-Purvis, Jason K Cullen, Carol Walker, Adam WatsonAdam Watson, Antony CarrAntony Carr, Jo Murray, Timothy C HumphreyThe healing of broken chromosomes by de novo telomere addition, while a normal developmental process in some organisms, has the potential to cause extensive loss of heterozygosity, genetic disease, or cell death. However, it is unclear how de novo telomere addition (dnTA) is regulated at DNA double-strand breaks (DSBs). Here, using a non-essential minichromosome in fission yeast, we identify roles for the HR factors Rqh1 helicase, in concert with Rad55, in suppressing dnTA at or near a DSB. We find the frequency of dnTA in rqh1? rad55? cells is reduced following loss of Exo1, Swi5 or Rad51. Strikingly, in the absence of the distal homologous chromosome arm dnTA is further increased, with nearly half of the breaks being healed in rqh1? rad55? or rqh1? exo1? cells. These findings provide new insights into the genetic context of highly efficient dnTA within HR intermediates, and how such events are normally suppressed to maintain genome stability
Funding
Single Molecule Imaging of the DNA Damage Response in Live Cells; G0250; EUROPEAN UNION; 268788
Repair of replication-associated double strand breaks; G1100; BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL; BB/K019805/1
History
Publication status
- Published
File Version
- Published version
Journal
Nucleic Acids ResearchISSN
0305-1048Publisher
Oxford University PressExternal DOI
Page range
1-14Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Research groups affiliated with
- Genome Damage and Stability Centre Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2020-01-28First Open Access (FOA) Date
2020-01-28First Compliant Deposit (FCD) Date
2020-01-28Usage metrics
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