Related Experiment Video
Updated: Jan 28, 2026
Preparation of Meiotic Chromosome Spreads from Zebrafish Spermatocytes
Published on: March 3, 2020
Persistent DNA-break potential near telomeres increases initiation of meiotic recombination on short chromosomes
Vijayalakshmi V Subramanian1, Xuan Zhu2,3, Tovah E Markowitz1,4
1Department of Biology, New York University, New York, NY, 10003, USA.
Abstract:
Faithful meiotic chromosome inheritance and fertility rely on the stimulation of meiotic crossover recombination by potentially genotoxic DNA double-strand breaks (DSBs). To avoid excessive damage, feedback mechanisms down-regulate DSBs, likely in response to initiation of crossover repair. In Saccharomyces cerevisiae, this regulation requires the removal of the conserved DSB-promoting protein Hop1/HORMAD during chromosome synapsis. Here, we identify privileged end-adjacent regions (EARs) spanning roughly 100 kb near all telomeres that escape DSB down-regulation. These regions retain Hop1 and continue to break in pachynema despite normal synaptonemal complex deposition. Differential retention of Hop1 requires the disassemblase Pch2/TRIP13, which preferentially removes Hop1 from telomere-distant sequences, and is modulated by the histone deacetylase Sir2 and the nucleoporin Nup2. Importantly, the uniform size of EARs among chromosomes contributes to disproportionately high DSB and repair signals on short chromosomes in pachynema, suggesting that EARs partially underlie the curiously high recombination rate of short chromosomes.
Insights
Meiotic recombination relies on DNA double-strand breaks (DSBs). Certain telomere regions escape DSB regulation, retaining a key protein and leading to higher break rates on shorter chromosomes, impacting inheritance.
Area of Science:
- Genetics
- Molecular Biology
- Cell Biology
Background:
- Faithful chromosome inheritance during meiosis requires programmed DNA double-strand breaks (DSBs) to promote crossover recombination.
- Feedback mechanisms normally down-regulate DSBs to prevent genotoxicity, likely triggered by crossover repair initiation.
- In yeast, this regulation involves removing the DSB-promoting protein Hop1 (HORMAD) during chromosome synapsis.
Purpose of the Study:
- To investigate the regulation of DSBs during yeast meiosis.
- To identify regions of the chromosome that escape DSB down-regulation.
- To understand the mechanism and consequences of differential DSB regulation.
Main Methods:
- Analysis of DNA double-strand break (DSB) hotspots in Saccharomyces cerevisiae.
- Investigating the localization and function of the Hop1/HORMAD protein.
- Utilizing genetic manipulation of key regulatory proteins like Pch2/TRIP13, Sir2, and Nup2.
- Chromosome synapsis and DSB repair analysis.
Main Results:
- Identified end-adjacent regions (EARs) near telomeres that escape DSB down-regulation, retaining Hop1.
- These EARs exhibit persistent DSBs in pachytene even with normal synaptonemal complex formation.
- Differential Hop1 removal, mediated by Pch2/TRIP13 and modulated by Sir2 and Nup2, explains EARs.
- Uniform EAR size leads to disproportionately high DSB and repair signals on shorter chromosomes.
Conclusions:
- Telomere-proximal regions (EARs) represent exceptions to meiotic DSB down-regulation.
- The Pch2/TRIP13 disassemblase, influenced by Sir2 and Nup2, governs Hop1 retention in EARs.
- EARs contribute to the elevated recombination rates observed in shorter chromosomes, impacting meiotic fidelity.
Related Concept Videos
02:41Telomeres and Telomerase
02:40Chromosome Structure
The centromere is a DNA sequence that links sister chromatids. This is also where kinetochores, protein complexes to which spindle microtubules attach, are constructed after the chromosome is replicated. The kinetochores allow the spindle microtubules to move the chromosomes within the cell during cell division.
Telomeres consist of non-coding repetitive nucleotide...
01:09Recombinant DNA
02:31Chromosome Replication
02:04Fixing Double-strand Breaks
01:51Lampbrush Chromosomes
LBCs are made up of two pairs of conjugating homologous chromatids. Each chromatid consists of alternatively positioned regions of condensed-inactive chromatin and loosely placed-active side loops, which can be contracted and extended. The loops...