A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes.
A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes.
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DOI：
10.1038/s41467-021-24554-2
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发表时间：
2021-07-14
影响因子：
16.6
通讯作者：
Madgwick S
中科院分区：
文献类型：
--
作者：
Thomas C;Wetherall B;Levasseur MD;Harris RJ;Kerridge ST;Higgins JMG;Davies OR;Madgwick S
成功的细胞分裂依赖于及时去除关键的细胞周期蛋白，如securin。Securin抑制分离酶，分离酶切割将染色体连接在一起的粘蛋白环。Securin必须在分裂后期之前耗尽，以确保染色体分离在分裂后期发生。在这里，我们发现，在减数分裂I，小鼠卵母细胞含有过量的securin分离酶。我们揭示了一种机制，促进过度securin破坏前中期I。重要的是，这种机制依赖于securin的分离酶相互作用片段（SIS）内的两个苯丙氨酸残基，仅当securin不与分离酶结合时才暴露。我们认为，这些残基有利于去除非分离酶结合的securin提前中期，抑制这一时期的破坏突变两个残基导致大多数卵母细胞在减数分裂I停止。我们进一步提出，细胞securin水平超过量的卵母细胞是能够单独在中期删除，这样的前中期破坏机制，在这里确定的是必不可少的小鼠卵母细胞的正确减数分裂进程。Securin抑制蛋白酶分离酶，必须在分裂后期之前去除，以确保及时的染色体分离。在这里，作者定义了小鼠卵母细胞前中期I中securin破坏的机制，并证明了其对成功减数分裂进程的重要性。
Successful cell division relies on the timely removal of key cell cycle proteins such as securin. Securin inhibits separase, which cleaves the cohesin rings holding chromosomes together. Securin must be depleted before anaphase to ensure chromosome segregation occurs with anaphase. Here we find that in meiosis I, mouse oocytes contain an excess of securin over separase. We reveal a mechanism that promotes excess securin destruction in prometaphase I. Importantly, this mechanism relies on two phenylalanine residues within the separase-interacting segment (SIS) of securin that are only exposed when securin is not bound to separase. We suggest that these residues facilitate the removal of non-separase-bound securin ahead of metaphase, as inhibiting this period of destruction by mutating both residues causes the majority of oocytes to arrest in meiosis I. We further propose that cellular securin levels exceed the amount an oocyte is capable of removing in metaphase alone, such that the prometaphase destruction mechanism identified here is essential for correct meiotic progression in mouse oocytes. Securin inhibits the protease separase and must be removed before anaphase to ensure timely chromosome segregation. Here, the authors define a mechanism of securin destruction in prometaphase I in mouse oocytes and demonstrate its importance for successful meiotic progression.
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DOI：
10.1038/nrm3494
发表时间：
2013-01
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
16.8
作者：
Boland A;Martin TG;Zhang Z;Yang J;Bai XC;Chang L;Scheres SH;Barford D
通讯作者：
Barford D
DOI：
10.1016/j.cub.2015.12.073
发表时间：
2016-03-07
期刊：
Current biology : CB
影响因子：
--
作者：
Burkhardt S;Borsos M;Szydlowska A;Godwin J;Williams SA;Cohen PE;Hirota T;Saitou M;Tachibana-Konwalski K
通讯作者：
Tachibana-Konwalski K
影响因子：
3.8
作者：
Homer, HA;McDougall, A;Herbert, M
通讯作者：
Herbert, M
影响因子：
64.5
作者：
Ciosk, R;Zachariae, W;Nasmyth, K
通讯作者：
Nasmyth, K