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Title: Meiotic chromosome synapsis depends on multivalent SYCE1-SIX6OS1 interactions that are disrupted in cases of human infertility
Authors: Sáez, Fernando Sánchez
H, Laura Gómez
Dunne, Orla M
Keywords: Meiosis; SYCE1; SIX6OS1; Premature ovarian failure
Issue Date: 2020
Publisher: Biochemical Journal
Abstract: Meiotic reductional division is dependent on the synaptonemal complex (SC), a supramolecular protein assembly that mediates homologous chromosomes synapsis and promotes crossover formation. The mammalian SC is formed of eight structural components, including SYCE1, the only central element protein with known causative mutations in human infertility. We combine mouse genetics, cellular and biochemical studies to reveal that SYCE1 undergoes multivalent interactions with SC component SIX6OS1. The N-terminus of SIX6OS1 binds and disrupts SYCE1’s core dimeric structure to form a 1:1 complex, whilst their downstream sequences provide a distinct second interface. These interfaces are separately disrupted by SYCE1 mutations associated with non-obstructive azoospermia and premature ovarian failure, respectively. Mice harbouring SYCE1’s POF mutation and a targeted deletion within SIX6OS1’s N-terminus are infertile with failure of chromosome synapsis. We conclude that both SYCE1-SIX6OS1 binding interfaces are essential for SC assembly, thus explaining how SYCE1’s reported clinical mutations give rise to human infertility.
Description: Tài liệu này được phát hành theo giấy phép CC-BY 4.0
URI: http://dlib.hust.edu.vn/handle/HUST/24680
Link item primary: https://www.biorxiv.org/content/10.1101/2020.02.04.934372v1
Appears in Collections:OER - Kỹ thuật hóa học; Công nghệ sinh học - Thực phẩm; Công nghệ môi trường
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