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Meiotic chromosome synapsis depends on multivalent SYCE1-SIX6OS1 interactions that are disrupted in cases of human infertility

DOI: 10.1126/sciadv.abb1660 DOI Help

Authors: Fernando Sánchez-Sáez (CSIC-Universidad de Salamanca) , Laura Gómez-H (CSIC-Universidad de Salamanca) , Orla M. Dunne (Newcastle University) , Cristina Gallego-Páramo (Newcastle University) , Natalia Felipe-Medina (CSIC-Universidad de Salamanca) , Manuel Sánchez-Martín (Universidad de Salamanca) , Elena Llano (Universidad de Salamanca) , Alberto M. Pendas (CSIC-Universidad de Salamanca) , Owen R. Davies (Newcastle University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science Advances , VOL 6

State: Published (Approved)
Published: September 2020
Diamond Proposal Number(s): 15836 , 21777 , 23510

Open Access Open Access

Abstract: 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.

Diamond Keywords: Infertility

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: B21-High Throughput SAXS

Added On: 01/10/2020 02:21

Documents:
eabb1660.full.pdf

Discipline Tags:

Life Sciences & Biotech Genetics Structural biology Chemistry Biochemistry

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)