Meiotic chromosome synapsis depends on multivalent SYCE1-SIX6OS1 interactions that are disrupted in cases of human infertility
| العنوان: | Meiotic chromosome synapsis depends on multivalent SYCE1-SIX6OS1 interactions that are disrupted in cases of human infertility |
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| المؤلفون: | Manuel Sánchez-Martín, Natalia Felipe-Medina, Laura Gómez-H, Alberto M. Pendás, Owen R. Davies, Elena Llano, Orla M. Dunne, Fernando Sánchez-Sáez, Cristina Gallego-Páramo |
| المساهمون: | Wellcome Trust, Royal Society (UK), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Junta de Castilla y León, European Commission |
| المصدر: | Sánchez-Sáez, F, Gómez-H, L, Dunne, O M, Gallego-Páramo, C, Felipe-Medina, N, Sánchez-Martín, M, Llano, E, Pendas, A M & Davies, O R 2020, ' Meiotic chromosome synapsis depends on multivalent SYCE1-SIX6OS1 interactions that are disrupted in cases of human infertility ', Science Advances, vol. 6, no. 36, eabb1660 . https://doi.org/10.1126/sciadv.abb1660 Digital.CSIC. Repositorio Institucional del CSIC instname Science Advances |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Infertility, ComputingMilieux_LEGALASPECTSOFCOMPUTING, Biology, medicine.disease_cause, Biochemistry, Mice, 03 medical and health sciences, 0302 clinical medicine, Meiosis, Genetics, Homologous chromosome, medicine, Animals, Humans, Central element, Research Articles, Azoospermia, 030304 developmental biology, Mammals, 0303 health sciences, Mutation, Multidisciplinary, Synaptonemal Complex, Synapsis, SciAdv r-articles, Chromosome, medicine.disease, Premature ovarian failure, Cell biology, ComputingMilieux_GENERAL, DNA-Binding Proteins, Chromosome Pairing, Synaptonemal complex, 030220 oncology & carcinogenesis, 030217 neurology & neurosurgery, Research Article |
| الوصف: | Copyright © 2020 The Authors. Meiotic reductional division depends on the synaptonemal complex (SC), a supramolecular protein assembly that mediates homologous chromosomes synapsis and promotes crossover formation. The mammalian SC has 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, while their downstream sequences provide a distinct second interface. These interfaces are separately disrupted by SYCE1 mutations associated with nonobstructive azoospermia and premature ovarian failure (POF), respectively. Mice harboring 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. O.R.D. is a Sir Henry Dale Fellow jointly funded by the Wellcome Trust and Royal Society (grant number 104158/Z/14/Z). This work was supported by MINECO (BFU2017-89408-R) and by Junta de Castilla y Leon (CSI239P18). F.S.-S., L.G.-H., and N.F.-M. are supported by European Social Fund/JCyLe grants (EDU/556/2019, EDU/1083/2013, and EDU/310/2015). CIC-IBMCC is supported by the Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia cofunded by the Castilla–León autonomous government and the European Regional Development Fund (CLC–2017–01). |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::68c07bb18a568d307c79d3dbec92b2a1 https://www.pure.ed.ac.uk/ws/files/211129427/eabb1660.full.pdf |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....68c07bb18a568d307c79d3dbec92b2a1 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |