biostudies-literatureUnknownDe Muyt ANICHD NIH HHSMeiotic crossovers are needed to produce genetically balanced gametes. In mammals, crossover formation is mediated by a conserved set of pro-crossover proteins via mechanisms that remain unclear. Here, we characterize a mammalian pro-crossover factor HEIP1. In mouse HEIP1 is essential for crossing over and fertility of both sexes. HEIP1 promotes crossing over by orchestrating the recruitment of other pro-crossover proteins, including the MutS<i>γ</i> complex (MSH4-MSH5) and E3 ligases (HEI10, RNF212, and RNF212B), that are required to mature crossover sites and recruit the crossover-specific resolution complex MutL<i>γ</i>. Moreover, HEIP1 directly interacts with HEI10, suggesting a direct role in controlling the recruitment of pro-crossover E3 ligases. During early stages of meiotic prophbioRxiv : the preprint server for biology2025.08.25.672081https://www.ebi.ac.uk/biostudies/studies/S-EPMC12407729biostudies-literatureHEIP1 orchestrates pro-crossover protein activity during mammalian meiosis.PMC12407729R01 HD109322Lee SRobert TMercier RBorde VDe Muyt AKhanal SAdam CHunter NToe LDfalseHEIP1 orchestrates pro-crossover protein activity during mammalian meiosis.Meiotic crossovers are needed to produce genetically balanced gametes. In mammals, crossover formation is mediated by a conserved set of pro-crossover proteins via mechanisms that remain unclear. Here, we characterize a mammalian pro-crossover factor HEIP1. In mouse HEIP1 is essential for crossing over and fertility of both sexes. HEIP1 promotes crossing over by orchestrating the recruitment of other pro-crossover proteins, including the MutS<i>γ</i> complex (MSH4-MSH5) and E3 ligases (HEI10, RNF212, and RNF212B), that are required to mature crossover sites and recruit the crossover-specific resolution complex MutL<i>γ</i>. Moreover, HEIP1 directly interacts with HEI10, suggesting a direct role in controlling the recruitment of pro-crossover E3 ligases. During early stages of meiotic proph2025-01-01T00:00:00Z2025 Aug2026-04-23T03:13:51.992Z2026-04-23T03:10:02.789ZS-EPMC124077294090973510.1101/2025.08.25.672081