A structural and biochemical study of human SYCP3 provides the first molecular model for the three-dimensional organisation that is imposed upon chromosomal DNA during meiosis and is essential for genetic exchange and fertility.
Building on previous work (Syrjänen, Pellegrini, & Davies, 2014), it is shown that SYCP3 contributes to the architecture of meiotic chromosomes through local bridging interactions that result in large-scale compaction of the chromosome axis.
Meiotic chromosome axis 'core' proteins from fungi, plants, and mammals form a conserved filament architecture, and use a common mechanism to recruit HORMAD proteins for meiotic recombination control.
Genetic and biochemical analysis reveal a variant in HSF2BP causing POI and C19ORF57/BRME1 as an interactor and stabilizer of HSF2BP by forming a complex with BRCA2, RAD51, RPA and PALB2.
Post-transcriptional control by YTHDC2 is required to turn off the mitotic proliferation program and facilitate proper expression of the meiotic program to allow a clean cell fate transition in the germline stem cell lineage.
Bilallelic mutations of FANCM, a DNA-damage response gene whose heterozygous mutations predispose to breast cancer, are involved in a familial case of Primary Ovarian Insufficiency establishing a link between infertility and cancer.
Biochemical and genetic approaches uncover a chromatin remodeler for PRDM9 binding and the parallel local epigenetic modification of cytosines in mouse spermatocytes.
ZCWPW1 has co-evolved with PRDM9, in particular the PRDM9-SET domain, and although not involved in PRDM9's role in positioning recombination events, it is required for PRDM9's role in pairing chromosomes.
The meiotic recombination landscape in vertebrates was re-engineered via the co-evolution of a dual histone H3K4/H3K36 methylation 'writer' PRDM9 and its 'reader' ZCWPW1 that facilitates efficient double strand break repair.
