Cohesin cleavage by separase is enhanced by a substrate motif distinct from the cleavage site

Rosen, Laura E.; Klebba, Joseph E.; Asfaha, Jonathan B.; Ghent, Chloe M.; Campbell, Melody G.; Cheng, Yifan; Morgan, David

doi:10.1038/s41467-019-13209-y

Cited by 26 publications

(12 citation statements)

References 41 publications

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“…Even in α kleisins and separase, several additional matches to the cleavage consensus are not cleaved by separase. An independent separase docking site was recently shown to contribute to cleavage efficiency in the budding yeast α kleisin Scc1 [63]. Matches to the corresponding motif ([L/V/ I/M]PE) are absent from UNO, THR, and MNM, but one is present in SNM.…”

Section: Plos Geneticsmentioning

confidence: 99%

Chromosome separation during Drosophila male meiosis I requires separase-mediated cleavage of the homolog conjunction protein UNO

et al. 2020

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Regular chromosome segregation during the first meiotic division requires prior pairing of homologous chromosomes into bivalents. During canonical meiosis, linkage between homologous chromosomes is maintained until late metaphase I by chiasmata resulting from meiotic recombination in combination with distal sister chromatid cohesion. Separasemediated elimination of cohesin from chromosome arms at the end of metaphase I permits terminalization of chiasmata and homolog segregation to opposite spindle poles during anaphase I. Interestingly, separase is also required for bivalent splitting during meiosis I in Drosophila males, where homologs are conjoined by an alternative mechanism independent of meiotic recombination and cohesin. Here we report the identification of a novel alternative homolog conjunction protein encoded by the previously uncharacterized gene univalents only (uno). The univalents that are present in uno null mutants at the start of meiosis I, instead of normal bivalents, are segregated randomly. In wild type, UNO protein is detected in dots associated with bivalent chromosomes and most abundantly at the localized pairing site of the sex chromosomes. UNO is cleaved by separase. Expression of a mutant UNO version with a non-functional separase cleavage site restores homolog conjunction in a uno null background. However, separation of bivalents during meiosis I is completely abrogated by this non-cleavable UNO version. Therefore, we propose that homolog separation during Drosophila male meiosis I is triggered by separase-mediated cleavage of UNO.

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Section: Plos Geneticsmentioning

confidence: 99%

Chromosome separation during Drosophila male meiosis I requires separase-mediated cleavage of the homolog conjunction protein UNO

et al. 2020

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“…Separase requires securin for its stability and full activity ( Hornig et al, 2002 ; Jallepalli et al, 2001 ; Rosen et al, 2019 ), and securin starts to associate with separase during separase translation ( Hellmuth et al, 2015 ). Hence a failure to establish this interaction may lead to reduced separase translation.…”

Section: Discussionmentioning

confidence: 99%

Cdc48 influence on separase levels is independent of mitosis and suggests translational sensitivity of separase

2022

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“…Separase requires securin for its stability and full activity (Hornig et al, 2002;Jallepalli et al, 2001;Rosen et al, 2019) and securin starts to associate with separase during separase translation (Hellmuth et al, 2015). Hence a failure of establishing this interaction may lead to reduced separase translation.…”

Section: Discussionmentioning

confidence: 99%

Cdc48 influence on separase levels is independent of mitosis and suggests translational sensitivity of separase

Vijayakumari

Müller

Hauf

2021

Preprint

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Cdc48 (p97/VCP) is a AAA-ATPase that can extract ubiquitinated proteins from their binding partners and channel substrates to the proteasome. A fission yeast cdc48 mutant (cdc48-353) shows low levels of the cohesin protease, separase, and pronounced chromosome segregation defects in mitosis. Separase initiates chromosome segregation when its binding partner securin is ubiquitinated and degraded. The low separase levels in the cdc48-353 mutant have been attributed to a failure to extract ubiquitinated securin from separase resulting in co-degradation of separase along with securin. If true, this establishes Cdc48 as a key regulator of mitosis. In contrast, we show here that low separase levels in the cdc48-353 mutant are independent of mitosis. Moreover, we find no evidence of enhanced separase degradation in the mutant. Instead, we suggest that the cdc48-353 mutant uncovers specific requirements for separase translation. Our results highlight a need to better understand how this key mitotic enzyme is synthesized.

show abstract

Cohesin cleavage by separase is enhanced by a substrate motif distinct from the cleavage site

Cited by 26 publications

References 41 publications

Chromosome separation during Drosophila male meiosis I requires separase-mediated cleavage of the homolog conjunction protein UNO

Chromosome separation during Drosophila male meiosis I requires separase-mediated cleavage of the homolog conjunction protein UNO

Cdc48 influence on separase levels is independent of mitosis and suggests translational sensitivity of separase

Cdc48 influence on separase levels is independent of mitosis and suggests translational sensitivity of separase

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