# Active maintenance of meiosis-specific chromosome structures in Caenorhabditis elegans by the deubiquitinase DUO-1

## TL;DR

This study shows that the enzyme DUO-1 in C. elegans is essential for maintaining proper chromosome structures during meiosis, which is crucial for successful reproduction.

## Contribution

The study identifies DUO-1 as a key deubiquitinase required for maintaining meiosis-specific chromosome architecture in C. elegans.

## Key findings

- Loss of DUO-1 leads to impaired assembly and instability of meiotic chromosome axes and synaptonemal complexes.
- DUO-1 is required throughout meiotic prophase to maintain chromosome compaction and promote proper segregation.
- Defects in DUO-1 function correlate with cohesin depletion and accumulation of DNA repair intermediates.

## Abstract

Faithful inheritance of chromosomes during reproduction requires assembly, remodeling, and disassembly of meiosis-specific chromosome structures, accompanied by dramatic changes in chromosome compaction. These features accompany the formation and release of temporary connections between homologous chromosomes that enable them to segregate to opposite spindle poles. Failure to properly coordinate these processes can result in improper chromosome segregation, producing aneuploid gametes and inviable zygotes. Here, we identify Caenorhabditis elegans DUO-1, an ortholog of mammalian ubiquitin-specific proteases, as a key mediator of these dynamic chromosomal events during meiotic prophase. Together, our data implicate DUO in mechanisms that promote reproductive success by actively maintaining meiosis-specific chromosome architecture throughout meiotic prophase.

Meiotic prophase is characterized by a dynamic program in which germ cells undergo a complex series of associations and dissociations of protein complexes that drive assembly, remodeling, and disassembly of meiosis-specific chromosome structures and dramatic changes in chromosome compaction. Failure to properly coordinate these processes can result in improper chromosome segregation, producing aneuploid gametes and inviable zygotes. Here, we investigate the roles of Caenorhabditis elegans DUO-1, an ortholog of mammalian ubiquitin-specific proteases USP26 and USP29, in mediating these dynamic chromosomal events during meiotic prophase. Cytological analyses of duo-1 null mutants indicate that loss of DUO-1 function leads to impaired assembly of meiotic chromosome axes and synaptonemal complexes (SCs), loss of integrity of meiotic chromosome axes, ineffective homolog pairing, premature separation of sister chromatids, and late-prophase chromosome decompaction. Further, axis/SC instability in duo-1 mutants correlates with depletion of REC-8 cohesin complexes and is accompanied by massive accumulation of early DSB repair intermediates. By using a dual-AID-tagged allele to deplete DUO-1 during meiotic development, we demonstrate that DUO-1 is continually required throughout meiotic prophase progression, to promote proper axis/SC assembly in early prophase, to maintain axis/SC stability during the late pachytene stage, and to promote/maintain chromosome compaction at the end of meiotic prophase. Together, our data emphasize the importance of mechanisms that actively maintain meiotic chromosome structure and meiosis-specific chromosome architecture throughout meiotic prophase and implicate DUO-1 as a key player in these active maintenance processes.