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

Abstract 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 DN...

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Veröffentlicht in:	Nucleic acids research Jg. 48; H. 3; S. 1271 - 1284
Hauptverfasser:	Davé, 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, Humphrey, Timothy C
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	England Oxford University Press 20.02.2020
Schlagworte:	Chromosomes, Fungal - genetics DNA Breaks, Double-Stranded DNA Helicases - genetics DNA-Binding Proteins - genetics Exodeoxyribonucleases - genetics Gene Expression Regulation, Fungal - genetics Genome Integrity, Repair and Genome, Fungal - genetics Genomic Instability - genetics Loss of Heterozygosity - genetics Rad51 Recombinase - genetics Recombinational DNA Repair - genetics Schizosaccharomyces - genetics Schizosaccharomyces pombe Proteins - genetics Telomere - genetics
ISSN:	0305-1048, 1362-4962, 1362-4962
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Zusammenfassung:	Abstract 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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0305-1048 1362-4962 1362-4962
DOI:	10.1093/nar/gkz1109