Biology subjects

Wellard, S. R.

Publications and source records attributed to Wellard, S. R..

3 recordsLinked to original sources

bioRxiv2023

MAP9/MAPH-9 supports axonemal microtubule doublets and modulates motor movement

Microtubule doublets (MTDs) are a well conserved compound microtubule structure found primarily in cilia. However, the mechanisms by which MTDs form and are maintained in vivo remain poorly understood. Here, we characterize microtubule-associated protein 9 (MAP9) as a novel MTD-associated protein. We demonstrate that C. elegans MAPH-9, a MAP9 homolog, is present during MTD assembly and localizes exclusively to MTDs, a preference that is in part mediated by tubulin polyglutamylation. Loss of MAPH-9 caused ultrastructural MTD defects, dysregulated axonemal motor velocity, and perturbed cilia function. As we found that the mammalian ortholog MAP9 localized to axonemes in cultured mammalian cells and mouse tissues, we propose that MAP9/MAPH-9 plays a conserved role in supporting the structure of axonemal MTDs and regulating ciliary motors.

cell biology↗

bioRxiv2020

Germline DNA replication shapes the recombination landscape in mammals

SummaryGenetic recombination generates novel trait combinations and understanding how recombination is distributed across the genome is key to modern genetics. The PRDM9 protein defines recombination hotspots, however megabase-scale recombination patterning is independent of PRDM9. The single round of DNA replication, which precedes recombination in meiosis, may establish these patterns, therefore we devised a novel approach to study meiotic replication that includes robust and sensitive mapping of replication origins. We find that meiotic DNA replication is distinct; reduced origin firing slows replication in meiosis and a distinctive replication pattern in human males underlies the sub-telomeric increase in recombination. We detected a robust correlation between replication and both contemporary and ancestral recombination and found that replication origin density coupled with chromosome size determines the recombination potential of individual chromosomes. Our findings and methods have far-reaching implications for understanding the mechanisms underlying DNA replication, genetic recombination, and the landscape of mammalian germline variation.

genomics↗

bioRxiv2019

Aurora B and C kinases regulate prophase exit and chromosome segregation during spermatogenesis

Precise control of chromosome dynamics during meiosis is critical for fertility. A gametocyte undergoing meiosis coordinates formation of the synaptonemal complex (SC) to promote efficient homologous chromosome recombination. Subsequent disassembly of the SC is required prior to meiotic divisions to ensure accurate segregation of chromosomes. We examined the requirements of the mammalian Aurora kinases (AURKA, B, and C) during SC disassembly and chromosome segregation using a combination of chemical inhibition and gene deletion approaches. We find that both mouse and human spermatocytes fail to disassemble SC lateral elements when AURKB and AURKC are inhibited. Interestingly, both Aurkb conditional knockout and Aurkc knockout spermatocytes successfully progress through meiosis and mice are fertile. In contrast, Aurkb, Aurkc double knockout spermatocytes failed to coordinate disassembly of SC lateral elements with chromosome segregation, resulting in delayed meiotic progression, spindle assembly checkpoint failure, chromosome missegregation, and abnormal spermatids. Collectively, our data demonstrates that AURKB and AURKC functionally compensate for one another ensuring successful mammalian spermatogenesis. SUMMARYChemical inhibition and gene deletion approaches show that Aurora B and Aurora C have overlapping functions that ensure timely disassembly of lateral element components of the synaptonemal complex in mouse and human spermatocytes and ensure accurate chromosome segregation during meiosis.

cell biology↗