Chromosome Axis Defects Induce a Checkpoint-Mediated Delay and Interchromosomal Effect on Crossing Over during Drosophila Meiosis
Open Access
- 12 August 2010
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Genetics
- Vol. 6 (8), e1001059
- https://doi.org/10.1371/journal.pgen.1001059
Abstract
Crossovers mediate the accurate segregation of homologous chromosomes during meiosis. The widely conserved pch2 gene of Drosophila melanogaster is required for a pachytene checkpoint that delays prophase progression when genes necessary for DSB repair and crossover formation are defective. However, the underlying process that the pachytene checkpoint is monitoring remains unclear. Here we have investigated the relationship between chromosome structure and the pachytene checkpoint and show that disruptions in chromosome axis formation, caused by mutations in axis components or chromosome rearrangements, trigger a pch2-dependent delay. Accordingly, the global increase in crossovers caused by chromosome rearrangements, known as the “interchromosomal effect of crossing over,” is also dependent on pch2. Checkpoint-mediated effects require the histone deacetylase Sir2, revealing a conserved functional connection between PCH2 and Sir2 in monitoring meiotic events from Saccharomyces cerevisiae to a metazoan. These findings suggest a model in which the pachytene checkpoint monitors the structure of chromosome axes and may function to promote an optimal number of crossovers. Meiosis is a specialized cell division in which diploid organisms form haploid gametes for sexual reproduction. This is accomplished by a single round of replication followed by two consecutive divisions. At the first meiotic division, the segregation of homologous chromosomes in most organisms is dependent upon genetic recombination, or crossing over. Crossing over must therefore be regulated to ensure that every pair of homologous chromosomes receives at least one reciprocal exchange. Homologous chromosomes that do not receive a crossover frequently undergo missegregation, yielding gametes that do not contain the normal chromosome number, conditions frequently associated in humans with infertility and birth defects. The pch2 gene is widely conserved and in Drosophila melanogaster is required for a meiosis-specific checkpoint that delays progression when crossover formation is defective. However, the underlying process that the checkpoint is monitoring remains unclear. Here we show that defects in axis components and homolog alignment are sufficient to induce checkpoint activity and increase crossing over across the genome. Based on these observations, we hypothesize that the checkpoint may monitor the integrity of chromosome axes and function to promote an optimal number of crossovers during meiosis.This publication has 45 references indexed in Scilit:
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