PDS5 proteins regulate the length of axial elements and telomere integrity during male mouse meiosis

Abstract

Cohesin cofactors regulate the loading, maintenance and release of cohesin complexes from chromosomes during the mitotic cell cycle but little is known on their role during vertebrate meiosis. One such cofactor is PDS5, which exists in two versions in somatic and germline cells, PDS5A and PDS5B, with unclear functional specificity. Here we have analyzed their distribution and functions in mouse spermatocytes. We show that simultaneous elimination of PDS5A and PDS5B results in severe defects during prophase I while their individual depletion does not, suggesting a functional redundancy of the two factors. Shortened axial/lateral elements and a reduction of early recombination nodules are observed in the absence of both PDS5 proteins. Moreover, telomere integrity and their association to the nuclear envelope are severely compromised. As these defects occur without detectable reduction in chromosome-bound cohesin, we propose that the dynamic behavior of the complex, mediated by PDS5 proteins, is key for successful completion of meiotic prophase I.

Chromosome Organization in Early Meiotic Prophase

“…Interestingly, axis length can also be impacted by the dynamic behavior of cohesin complexes. Indeed, the concomitant depletion of the cohesin regulators PDS5A and PDS5B leads to a severe shortening of axial elements, despite the presence of all tested cohesin subunits in those spermatocytes (Viera et al, 2020). This role of Pds5 in controlling axis length as also been observed in S. cerevisiae (Jin et al, 2009;Song et al, 2021) and even in the absence of the sister chromatid (Hong et al, 2019).…”

“…SYCP2 is not detected on axes in the absence of SYCP3. also colocalizes with telomeres in all stages of prophase I (Viera et al, 2020). Conditional depletion of either PDS5A or PDS5B does not alter progression through prophase I.…”

“…By mid-pachytene PDS5A disperses on the chromatin, with no staining detected on lateral axial elements. Later, at metaphase I and II, PDS5A reappears at centromeres ( Viera et al, 2020 ). PDS5B has a partly different localization pattern, it is detected earlier (early leptotene) and remains longer (late pachytene) at axial elements where it colocalizes with REC8, and partially with SYCP3 ( Viera et al, 2020 ).…”

“…Later, at metaphase I and II, PDS5A reappears at centromeres ( Viera et al, 2020 ). PDS5B has a partly different localization pattern, it is detected earlier (early leptotene) and remains longer (late pachytene) at axial elements where it colocalizes with REC8, and partially with SYCP3 ( Viera et al, 2020 ). Co-immunoprecipitation assays corroborate this finding, showing that PDS5B interacts with the axis-related proteins SMC1β, SYCP2, and HORMAD1 ( Fukuda et al, 2010 ).…”

Interplay between Pds5 and Rec8 in regulating chromosome axis length and crossover frequency

“…However, whether and how Pds5 works with cohesin to modulate the chromosome axis is poorly understood. Moreover, meiotic depletion of Pds5 results in decreased homolog pairing and recombination frequencies (22,23,27,28). We are also interested to investigate how Pds5 regulates these processes.…”