Drosophila PCH2 Is Required for a Pachytene Checkpoint That Monitors Double-Strand-Break-Independent Events Leading to Meiotic Crossover Formation
- 1 January 2009
- journal article
- Published by Oxford University Press (OUP) in Genetics
- Vol. 181 (1), 39-51
- https://doi.org/10.1534/genetics.108.093112
Abstract
During meiosis, programmed DNA double-strand breaks (DSBs) are repaired to create at least one crossover per chromosome arm. Crossovers mature into chiasmata, which hold and orient the homologous chromosomes on the meiotic spindle to ensure proper segregation at meiosis I. This process is usually monitored by one or more checkpoints that ensure that DSBs are repaired prior to the meiotic divisions. We show here that mutations in Drosophila genes required to process DSBs into crossovers delay two important steps in meiotic progression: a chromatin-remodeling process associated with DSB formation and the final steps of oocyte selection. Consistent with the hypothesis that a checkpoint has been activated, the delays in meiotic progression are suppressed by a mutation in the Drosophila homolog of pch2. The PCH2-dependent delays also require proteins thought to regulate the number and distribution of crossovers, suggesting that this checkpoint monitors events leading to crossover formation. Surprisingly, two lines of evidence suggest that the PCH2-dependent checkpoint does not reflect the accumulation of unprocessed recombination intermediates: the delays in meiotic progression do not depend on DSB formation or on mei-41, the Drosophila ATR homolog, which is required for the checkpoint response to unrepaired DSBs. We propose that the sites and/or conditions required to promote crossovers are established independently of DSB formation early in meiotic prophase. Furthermore, the PCH2-dependent checkpoint is activated by these events and pachytene progression is delayed until the DSB repair complexes required to generate crossovers are assembled. Interestingly, PCH2-dependent delays in prophase may allow additional crossovers to form.Keywords
This publication has 53 references indexed in Scilit:
- Yeast Pch2 promotes domainal axis organization, timely recombination progression, and arrest of defective recombinosomes during meiosisProceedings of the National Academy of Sciences of the United States of America, 2008
- Minichromosome Maintenance Proteins Interact with Checkpoint and Recombination Proteins To Promote S-Phase Genome StabilityMolecular and Cellular Biology, 2008
- Mouse Pachytene Checkpoint 2 (Trip13) Is Required for Completing Meiotic Recombination but Not SynapsisPLoS Genetics, 2007
- A Novel NonnullZIP1Allele Triggers Meiotic Arrest With Synapsed Chromosomes inSaccharomyces cerevisiaeGenetics, 2007
- Drosophila ATR in Double-Strand Break RepairGenetics, 2007
- Two Distinct Surveillance Mechanisms Monitor Meiotic Chromosome Metabolism in Budding YeastCurrent Biology, 2006
- Drosophila mus301/spindle-C Encodes a Helicase With an Essential Role in Double-Strand DNA Break Repair and Meiotic ProgressionGenetics, 2006
- A Link between Meiotic Prophase Progression and Crossover ControlPLoS Genetics, 2006
- Temporal Analysis of Meiotic DNA Double-Strand Break Formation and Repair in Drosophila FemalesPLoS Genetics, 2006
- REC, Drosophila MCM8, Drives Formation of Meiotic CrossoversPLoS Genetics, 2005