Regulation Mechanisms of Meiotic Recombination Revealed from the Analysis of a Fission Yeast Recombination Hotspot ade6-M26

Abstract

Meiotic recombination is a pivotal event that ensures faithful chromosome segregation and creates genetic diversity in gametes. Meiotic recombination is initiated by programmed double-strand breaks (DSBs), which are catalyzed by the conserved Spo11 protein. Spo11 is an enzyme with structural similarity to topoisomerase II and induces DSBs through the nucleophilic attack of the phosphodiester bond by the hydroxy group of its tyrosine (Tyr) catalytic residue. DSBs caused by Spo11 are repaired by homologous recombination using homologous chromosomes as donors, resulting in crossovers/chiasmata, which ensure physical contact between homologous chromosomes. Thus, the site of meiotic recombination is determined by the site of the induced DSB on the chromosome. Meiotic recombination is not uniformly induced, and sites showing high recombination rates are referred to as recombination hotspots. In fission yeast, ade6-M26, a nonsense point mutation of ade6 is a well-characterized meiotic recombination hotspot caused by the heptanucleotide sequence 5′-ATGACGT-3′ at the M26 mutation point. In this review, we summarize the meiotic recombination mechanisms revealed by the analysis of the fission ade6-M26 gene as a model system.

Metabolic stress-induced long ncRNA transcription governs the formation of meiotic DNA breaks in the fission yeast fbp1 gene

“…This DSB induction under environmental stress is mediated The formation of meiotic DSBs in fbp1 upon glucose starvation is dependent upon the Atf1-Pcr1 transcription factor (Fig 4). The ade6-M26 meiotic recombination hotspot is also an Atf1-Pcr1 transcription factor mediated-hotspot (reviewed in [11]), but not in a glucose-regulated manner. It remains unclear how cells select meiotic recombination hotspots among the numerous Atf1-Pcr1 binding sites.…”

“…Meiotic recombination is initiated by the formation of double-strand breaks (DSBs) catalyzed by the conserved topoisomerase-like Spo11 protein (Rec12 in the fission yeast Schizosaccharomyces pombe ) [ 11 , 12 ]. The distribution of meiotic DSBs on the chromosome is not equivalent but clustered at hotspots.…”

“…Generally, chromatin structure plays a critical role in determining the transcription status, as the access of trans -acting factors to their target DNA is restricted by the tightly positioned chromatin [ 33 , 34 ], and thus open (nucleosome-free) and closed (nucleosome-condensed) chromatin states are usually associated with transcriptional activation and gene silencing, respectively. In addition to this control, chromatin structure also plays a critical role in determining the sites of meiotic DSB formation, as the access of Spo11 to the target DNA is also restricted by tightly positioned nucleosomes [ 11 , 35 – 40 ]. This view supports the hypothesis that transcriptional responses to various stresses during meiosis can affect the location of meiotic DSBs.…”