HEIP1 is required for efficient meiotic crossover implementation and is conserved from plants to humans

Proc Natl Acad Sci U S A. 2023 Jun 6;120(23):e2221746120. doi: 10.1073/pnas.2221746120. Epub 2023 May 30.

Abstract

Crossovers (CO) shuffle genetic information and physically connect homologous chromosomal pairs, ensuring their balanced segregation during meiosis. COs arising from the major class I pathway require the activity of the well-conserved group of ZMM proteins, which, in conjunction with MLH1, facilitate the maturation of DNA recombination intermediates specifically into COs. The HEI10 Interacting Protein 1 (HEIP1) was identified in rice and proposed to be a new, plant-specific member of the ZMM group. Here, we establish and decipher the function of the Arabidopsis thaliana HEIP1 homolog in meiotic crossover formation and report its wide conservation in eukaryotes. We show that the loss of Arabidopsis HEIP1 elicits a marked reduction in meiotic COs and their redistribution toward chromosome ends. Epistasis analysis showed that AtHEIP1 acts specifically in the class I CO pathway. Further, we show that HEIP1 acts both prior to crossover designation, as the number of MLH1 foci is reduced in heip1, and at the maturation step of MLH1-marked sites into COs. Despite the HEIP1 protein being predicted to be primarily unstructured and very divergent at the sequence level, we identified homologs of HEIP1 in an extensive range of eukaryotes, including mammals.

Keywords: HEIP1; crossover; meiosis; recombination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arabidopsis* / genetics
  • Arabidopsis* / metabolism
  • Crossing Over, Genetic* / genetics
  • Humans
  • Mammals
  • Meiosis / genetics