PDS 5 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 mitosis but little is known on their role during vertebrate meiosis. One such cofactor is PDS5, which exists as two paralogs in somatic and germline cells, PDS5A and PDS5B, with unclear functions. Here, we have analyzed their distribution and functions in mouse spermatocytes. We show that simultaneous excision of Pds5A and Pds5B results in severe defects during early prophase I while their individual depletion does not, suggesting their functional redundancy. Shortened axial/lateral elements and a reduction of early recombination nodules are observed after the strong depletion of PDS5A/B 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.

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

“…Therefore, alterations in Pds5 to modulate axis length are an efficient way of regulating recombination frequency. Pds5 is conserved because decreased axis length and recombination frequency have also been observed in fission yeast and mammals when Pds5 is depleted during meiosis ( 23 , 27 , 28 , 55 ).…”

“…The depletion of cohesin results in shorter axes during mammalian meiosis ( 20 , 24 , 25 ). Pds5 meiotic depletion mutants show shorter chromosome axis in budding and fission yeast meiosis and also in mammal spermatogenesis ( 22 , 27 , 28 ). Our current study demonstrates that Pds5 and Rec8 dosage-dependently regulate meiotic chromosome axes in budding yeast.…”

“…Pds5, an important cohesin regulator, localizes on chromosome axes during meiotic prophase I ( 22 , 27 – 29 ). Meiosis-specific depletion of Pds5 during meiosis results in markedly short chromosome axes in budding yeast, fission yeast, and male mouse ( 22 , 27 , 28 ). Currently, the prevailing view is that Pds5 regulates the chromosome axis by modulating cohesin ( 27 , 30 ).…”

“…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.…”

PDS5A and PDS5B in Cohesin Function and Human Disease

“…PDS5A and PDS5B have their unique and redundant functions in the cell cycle, and depletion of both proteins will cause severe defects or cell death [ 75 , 93 , 96 , 182 ]. The redundant function of PDS5A and PDS5B provides a possibility to develop a therapeutic approach by using a synthetic lethal strategy.…”