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Peer-reviewedCC BY 4.0Nucleic Acids Research

RMI2 regulates recombination intermediate metabolism to ensure proper chromosome segregation in mammalian meiosis

  • Luciana Previato de Almeida1
  • Tolkappiyan Premkumar2,3
  • Monika K Kawecka1,4
  • Irma Gryniuk1,4
  • Agustin Carbajal1
  • Francesca Cole2,3
  • Roberto J Pezza1,4
4 affiliations
  1. 1Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation , Oklahoma City, OK 73104 ,
  2. 2Department of Epigenetics and Molecular Carcinogenesis, Division of Basic Sciences, The University of Texas MD Anderson Cancer Center , Houston, TX 77030 ,
  3. 3UTHealth Houston Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center , Houston, TX 77030 ,
  4. 4Department of Cell Biology, University of Oklahoma Health Sciences Center , Oklahoma City, OK 73104 ,
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Abstract

Proper segregation of meiotic chromosomes depends on the controlled formation and resolution of recombination intermediates that give rise to crossovers (COs). While the BTRR complex—comprising the BLM helicase, topoisomerase IIIα, and the proteins RMI1 and RMI2—is a well-characterized regulator of recombination in somatic cells, its function during meiosis remains incompletely understood, particularly for RMI2 in mammals. Here, we investigate the role of RMI2 in mouse spermatogenesis using a targeted RMI2 knockout model. Loss of RMI2 results in severe meiotic defects, including reduced testis size, increased apoptosis at the metaphase–anaphase I transition, and frequent chromosomal abnormalities such as lagging chromosomes in metaphase I cells and anaphase I chromatin bridges. Cytological analyses reveal disruptions in the processing of recombination intermediates. Our work monitoring molecular recombination outcomes at known recombination hotspots suggests that RMI2 regulates the balance of recombination pathways, constrains aberrant branch migration, and ensures proper CO maturation. Our findings show previously unappreciated functions for RMI2 essential for coordinating recombination intermediate metabolism and promoting proper chromosome conformation and segregation during meiosis. These results provide insights into the complex regulation of recombination intermediate homeostasis in higher eukaryotes and highlight the role of RMI2 in maintaining genome stability and proper gamete development in mammals.

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Cite

BibTeXRIS
BibTeX
@article{almeida2026rmi2,
  title = {{RMI2 regulates recombination intermediate metabolism to ensure proper chromosome segregation in mammalian meiosis}},
  author = {Luciana Previato de Almeida and Tolkappiyan Premkumar and Monika K Kawecka and Irma Gryniuk and Agustin Carbajal and Francesca Cole and Roberto J Pezza},
  journal = {Nucleic Acids Research},
  year = {2026},
  month = oct,
  doi = {10.1093/nar/gkag950},
  url = {https://academic.oup.com/nar/article/doi/10.1093/nar/gkag950/8863815},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - RMI2 regulates recombination intermediate metabolism to ensure proper chromosome segregation in mammalian meiosis
AU  - Luciana Previato de Almeida
AU  - Tolkappiyan Premkumar
AU  - Monika K Kawecka
AU  - Irma Gryniuk
AU  - Agustin Carbajal
AU  - Francesca Cole
AU  - Roberto J Pezza
PY  - 2026
DA  - 2026/10/05
JO  - Nucleic Acids Research
DO  - 10.1093/nar/gkag950
UR  - https://academic.oup.com/nar/article/doi/10.1093/nar/gkag950/8863815
AB  - Proper segregation of meiotic chromosomes depends on the controlled formation and resolution of recombination intermediates that give rise to crossovers (COs). While the BTRR complex—comprising the BLM helicase, topoisomerase IIIα, and the proteins RMI1 and RMI2—is a well-characterized regulator of recombination in somatic cells, its function during meiosis remains incompletely understood, particularly for RMI2 in mammals. Here, we investigate the role of RMI2 in mouse spermatogenesis using a targeted RMI2 knockout model. Loss of RMI2 results in severe meiotic defects, including reduced testis size, increased apoptosis at the metaphase–anaphase I transition, and frequent chromosomal abnormalities such as lagging chromosomes in metaphase I cells and anaphase I chromatin bridges. Cytological analyses reveal disruptions in the processing of recombination intermediates. Our work monitoring molecular recombination outcomes at known recombination hotspots suggests that RMI2 regulates the balance of recombination pathways, constrains aberrant branch migration, and ensures proper CO maturation. Our findings show previously unappreciated functions for RMI2 essential for coordinating recombination intermediate metabolism and promoting proper chromosome conformation and segregation during meiosis. These results provide insights into the complex regulation of recombination intermediate homeostasis in higher eukaryotes and highlight the role of RMI2 in maintaining genome stability and proper gamete development in mammals.
SN  - 0305-1048
SN  - 1362-4962
ER  -