Direct and Indirect Control of the Initiation of Meiotic Recombination by DNA Damage Checkpoint Mechanisms in Budding Yeast

Bilge Argunhan, Sarah Farmer, Wing Kit Leung, Yaroslav Terentyev, Neil Humphryes, Tomomi Tsubouchi, Hiroshi Toyoizumi, Hideo Tsubouchi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Meiotic recombination plays an essential role in the proper segregation of chromosomes at meiosis I in many sexually reproducing organisms. Meiotic recombination is initiated by the scheduled formation of genome-wide DNA double-strand breaks (DSBs). The timing of DSB formation is strictly controlled because unscheduled DSB formation is detrimental to genome integrity. Here, we investigated the role of DNA damage checkpoint mechanisms in the control of meiotic DSB formation using budding yeast. By using recombination defective mutants in which meiotic DSBs are not repaired, the effect of DNA damage checkpoint mutations on DSB formation was evaluated. The Tel1 (ATM) pathway mainly responds to unresected DSB ends, thus the sae2 mutant background in which DSB ends remain intact was employed. On the other hand, the Mec1 (ATR) pathway is primarily used when DSB ends are resected, thus the rad51 dmc1 double mutant background was employed in which highly resected DSBs accumulate. In order to separate the effect caused by unscheduled cell cycle progression, which is often associated with DNA damage checkpoint defects, we also employed the ndt80 mutation which permanently arrests the meiotic cell cycle at prophase I. In the absence of Tel1, DSB formation was reduced in larger chromosomes (IV, VII, II and XI) whereas no significant reduction was found in smaller chromosomes (III and VI). On the other hand, the absence of Rad17 (a critical component of the ATR pathway) lead to an increase in DSB formation (chromosomes VII and II were tested). We propose that, within prophase I, the Tel1 pathway facilitates DSB formation, especially in bigger chromosomes, while the Mec1 pathway negatively regulates DSB formation. We also identified prophase I exit, which is under the control of the DNA damage checkpoint machinery, to be a critical event associated with down-regulating meiotic DSB formation.

Original languageEnglish
Article numbere65875
JournalPLoS One
Volume8
Issue number6
DOIs
Publication statusPublished - 2013 Jun 10

Fingerprint

Saccharomycetales
Chromosomes
Meiotic Prophase I
DNA damage
Yeast
Genetic Recombination
DNA Damage
prophase
yeasts
chromosomes
DNA
mutants
cell cycle
Genome
mutation
Chromosome Breakage
Chromosome Segregation
Mutation
Genes
chromosome segregation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Argunhan, B., Farmer, S., Leung, W. K., Terentyev, Y., Humphryes, N., Tsubouchi, T., ... Tsubouchi, H. (2013). Direct and Indirect Control of the Initiation of Meiotic Recombination by DNA Damage Checkpoint Mechanisms in Budding Yeast. PLoS One, 8(6), [e65875]. https://doi.org/10.1371/journal.pone.0065875

Direct and Indirect Control of the Initiation of Meiotic Recombination by DNA Damage Checkpoint Mechanisms in Budding Yeast. / Argunhan, Bilge; Farmer, Sarah; Leung, Wing Kit; Terentyev, Yaroslav; Humphryes, Neil; Tsubouchi, Tomomi; Toyoizumi, Hiroshi; Tsubouchi, Hideo.

In: PLoS One, Vol. 8, No. 6, e65875, 10.06.2013.

Research output: Contribution to journalArticle

Argunhan, Bilge ; Farmer, Sarah ; Leung, Wing Kit ; Terentyev, Yaroslav ; Humphryes, Neil ; Tsubouchi, Tomomi ; Toyoizumi, Hiroshi ; Tsubouchi, Hideo. / Direct and Indirect Control of the Initiation of Meiotic Recombination by DNA Damage Checkpoint Mechanisms in Budding Yeast. In: PLoS One. 2013 ; Vol. 8, No. 6.
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