Homologous recombination repair intermediates promote efficient de novo telomere addition at DNA double-strand breaks

Dave, Anoushka, Pai, Chen-Chun, Durley, Samuel C, Hulme, Lydia, Sarkar, Sovan, Wee, Boon-Yu, Prudden, John, Tinline-Purvis, Helen, Cullen, Jason K, Walker, Carol, Watson, Adam, Carr, Antony M, Murray, Johanne M and Humphrey, Timothy C (2019) Homologous recombination repair intermediates promote efficient de novo telomere addition at DNA double-strand breaks. Nucleic Acids Research. pp. 1-14. ISSN 0305-1048

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The 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 rqh1Δ rad55Δ 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 rqh1Δ rad55Δ or rqh1Δ exo1Δ 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

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups: Genome Damage and Stability Centre
Subjects: Q Science
Q Science > Q Science (General)
Depositing User: Paula Amiet-West
Date Deposited: 28 Jan 2020 08:39
Last Modified: 19 Jul 2021 10:34
URI: http://sro.sussex.ac.uk/id/eprint/89612

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Project NameSussex Project NumberFunderFunder Ref
Single Molecule Imaging of the DNA Damage Response in Live CellsG0250EUROPEAN UNION268788
Repair of replication-associated double strand breaksG1100BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCILBB/K019805/1