Meiotic Recombination Intermediates Are Resolved with Minimal Crossover Formation during Return-to-Growth, an Analogue of the Mitotic Cell Cycle

Autor: Michael Lichten, Yaron Dayani, Giora Simchen
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: PLoS Genetics
PLoS Genetics, Vol 7, Iss 5, p e1002083 (2011)
ISSN: 1553-7404
1553-7390
Popis: Accurate segregation of homologous chromosomes of different parental origin (homologs) during the first division of meiosis (meiosis I) requires inter-homolog crossovers (COs). These are produced at the end of meiosis I prophase, when recombination intermediates that contain Holliday junctions (joint molecules, JMs) are resolved, predominantly as COs. JM resolution during the mitotic cell cycle is less well understood, mainly due to low levels of inter-homolog JMs. To compare JM resolution during meiosis and the mitotic cell cycle, we used a unique feature of Saccharomyces cerevisiae, return to growth (RTG), where cells undergoing meiosis can be returned to the mitotic cell cycle by a nutritional shift. By performing RTG with ndt80 mutants, which arrest in meiosis I prophase with high levels of interhomolog JMs, we could readily monitor JM resolution during the first cell division of RTG genetically and, for the first time, at the molecular level. In contrast to meiosis, where most JMs resolve as COs, most JMs were resolved during the first 1.5–2 hr after RTG without producing COs. Subsequent resolution of the remaining JMs produced COs, and this CO production required the Mus81/Mms4 structure-selective endonuclease. RTG in sgs1-ΔC795 mutants, which lack the helicase and Holliday junction-binding domains of this BLM homolog, led to a substantial delay in JM resolution; and subsequent JM resolution produced both COs and NCOs. Based on these findings, we suggest that most JMs are resolved during the mitotic cell cycle by dissolution, an Sgs1 helicase-dependent process that produces only NCOs. JMs that escape dissolution are mostly resolved by Mus81/Mms4-dependent cleavage that produces both COs and NCOs in a relatively unbiased manner. Thus, in contrast to meiosis, where JM resolution is heavily biased towards COs, JM resolution during RTG minimizes CO formation, thus maintaining genome integrity and minimizing loss of heterozygosity.
Author Summary Cell proliferation involves DNA replication followed by a mitotic division, producing two cells with identical genomes. Diploid organisms, which contain two genome copies per cell, also undergo meiosis, where DNA replication followed by two divisions produces haploid gametes, the equivalent sperm and eggs, with a single copy of the genome. During meiosis, the two copies of each chromosome are brought together and connected by recombination intermediates (joint molecules, JMs) at sites of sequence identity. During meiosis, JMs frequently resolve as crossovers, which exchange flanking sequences, and crossovers are required for accurate chromosome segregation. JMs also form during the mitotic cell cycle, but resolve infrequently as crossovers. To understand how JMs resolve during the mitotic cell cycle, we used a property of budding yeast, return to growth (RTG), in which cells exit meiosis and resume the mitotic cell cycle. By returning to growth cells with high levels of JMs, we determined how JMs resolve in a mitotic cell cycle-like environment. We found that, during RTG, most JMs are taken apart without producing crossovers by Sgs1, a DNA unwinding enzyme. Because Sgs1 is homologous to the mammalian BLM helicase, it is likely that similar mechanisms reduce crossover production in mammals.
Databáze: OpenAIRE
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