Chromosome-autonomous feedback down-regulates meiotic DNA break competence upon synaptonemal complex formation

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• Elevated DNA double-strand breaks (DSBs) occur in yeast mutants lacking synaptonemal complex (SC) and crossovers.
• These mutants suggest a loss of negative feedback inhibiting DSB formation upon homolog engagement.
• The chromosome-autonomous nature and triggers of this feedback remain uncharacterized.

Purpose of the Study:

• To investigate the chromosome-autonomous regulation of DSB formation during meiotic recombination.
• To determine the chromosomal processes recognized as 'homolog engagement'.
• To understand how aneuploidy affects meiotic DSB homeostasis.

Main Methods:

• Utilized karyotypically abnormal yeast strains (monosomic V, trisomy XV) to create localized homolog engagement defects.
• Analyzed DSB formation and Rec114 protein retention on specific chromosomes.
• Examined DSB numbers in SC-deficient, crossover-proficient mutants (ecm11, gmc2).

Main Results:

• Homolog engagement-defective chromosomes exhibited increased DSBs and prolonged Rec114 retention.
• These effects were chromosome-autonomous, leaving the rest of the genome unaffected.
• SC-deficient mutants showed DSB increases characteristic of homolog engagement defects.

Conclusions:

• Synaptonemal complex (SC) formation likely triggers DSB protein dissociation, reducing DSB competence.
• DSB number is regulated in a chromosome-autonomous manner during meiosis.
• Meiotic DSB homeostasis responds to aneuploidy, providing insights into chromosomal regulation.