Caenorhabditis elegans RMI2 functional homolog-2 (RMIF-2) and
RMI1 (RMH-1) have both overlapping and distinct meiotic
functions within the BTR complex

J 2021

Caenorhabditis elegans RMI2 functional homolog-2 (RMIF-2) and RMI1 (RMH-1) have both overlapping and distinct meiotic functions within the BTR complex

VELKOVA, M., Nicola SILVA, M. R. DELLO STRITTO, A. SCHLEIFFER, P. BARRAUD et. al.

Basic information

Original name

Caenorhabditis elegans RMI2 functional homolog-2 (RMIF-2) and RMI1 (RMH-1) have both overlapping and distinct meiotic functions within the BTR complex

Authors

VELKOVA, M., Nicola SILVA (380 Italy, belonging to the institution), M. R. DELLO STRITTO, A. SCHLEIFFER, P. BARRAUD, M. HARTL and V. JANTSCH (guarantor)

Edition

PLoS Genetics, San Francisco, Public Library of Science, 2021, 1553-7404

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10603 Genetics and heredity

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.020

RIV identification code

RIV/00216224:14110/21:00119145

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1371/journal.pgen.1009663

UT WoS

000674293300003

Keywords in English

Caenorhabditis elegans; RMIF-2; RMH-1; BTR complex

Abstract

V originále

Author summary Bloom syndrome is caused by mutations in proteins of the BTR complex (consisting of the Bloom helicase, topoisomerase 3, and the RMI1 and RMI2 scaffolding proteins) and the clinical characteristics are growth deficiency, short stature, skin photosensitivity, and increased cancer predisposition. At the cellular level, characteristic features are the presence of increased sister chromatid exchange on chromosomes; unresolved DNA recombination intermediates that eventually cause genome instability; and erroneous DNA repair by heterologous recombination (recombination between non-identical sequences, extremely rare in wild type animals), which can trigger translocations and chromosomal rearrangements. Identification of the Caenorhabditis elegans ortholog of RMI2 (called RMIF-2) allowed us to compare heterologous recombination in the germline of mutants of various BTR complex proteins. The heterologous recombination rate was several fold lower in rmif-2 mutants than in mutants of rmh-1 and him-6 (worm homologs of RMI1 and the Bloom helicase, respectively). Nevertheless, many phenotypic features point at RMIF-2 working together with RMH-1. If these germline functions of RMI2/RMIF-2 are conserved in humans, this might mean that individuals with RMI2 mutations have a lower risk of translocations and genome rearrangements than those with mutations in the other BTR complex genes. Homologous recombination is a high-fidelity repair pathway for DNA double-strand breaks employed during both mitotic and meiotic cell divisions. Such repair can lead to genetic exchange, originating from crossover (CO) generation. In mitosis, COs are suppressed to prevent sister chromatid exchange. Here, the BTR complex, consisting of the Bloom helicase (HIM-6 in worms), topoisomerase 3 (TOP-3), and the RMI1 (RMH-1 and RMH-2) and RMI2 scaffolding proteins, is essential for dismantling joint DNA molecules to form non-crossovers (NCOs) via decatenation. In contrast, in meiosis COs are essential for accurate chromosome segregation and the BTR complex plays distinct roles in CO and NCO generation at different steps in meiotic recombination. RMI2 stabilizes the RMI1 scaffolding protein, and lack of RMI2 in mitosis leads to elevated sister chromatid exchange, as observed upon RMI1 knockdown. However, much less is known about the involvement of RMI2 in meiotic recombination. So far, RMI2 homologs have been found in vertebrates and plants, but not in lower organisms such as Drosophila, yeast, or worms. We report the identification of the Caenorhabditis elegans functional homolog of RMI2, which we named RMIF-2. The protein shows a dynamic localization pattern to recombination foci during meiotic prophase I and concentration into recombination foci is mutually dependent on other BTR complex proteins. Comparative analysis of the rmif-2 and rmh-1 phenotypes revealed numerous commonalities, including in regulating CO formation and directing COs toward chromosome arms. Surprisingly, the prevalence of heterologous recombination was several fold lower in the rmif-2 mutant, suggesting that RMIF-2 may be dispensable or less strictly required for some BTR complex-mediated activities during meiosis.

Links

GA20-08819S, research and development project

Name: Pochopení úlohy PARG při podpoře tvorby a oprav dvouřetězcových zlomů DNA v meióze

Investor: Czech Science Foundation

Citovat

VELKOVA, M., Nicola SILVA, M. R. DELLO STRITTO, A. SCHLEIFFER, P. BARRAUD, M. HARTL and V. JANTSCH. Caenorhabditis elegans RMI2 functional homolog-2 (RMIF-2) and RMI1 (RMH-1) have both overlapping and distinct meiotic functions within the BTR complex. PLoS Genetics. San Francisco: Public Library of Science, 2021, vol. 17, No 7, p. 1-32. ISSN 1553-7404. Available from: https://dx.doi.org/10.1371/journal.pgen.1009663.

@article{1786884,
   author = {Velkova, M. and Silva, Nicola and Dello Stritto, M. R. and Schleiffer, A. and Barraud, P. and Hartl, M. and Jantsch, V.},
   article_location = {San Francisco},
   article_number = {7},
   doi = {http://dx.doi.org/10.1371/journal.pgen.1009663},
   keywords = {Caenorhabditis elegans; RMIF-2; RMH-1; BTR complex},
   language = {eng},
   issn = {1553-7404},
   journal = {PLoS Genetics},
   title = {Caenorhabditis elegans RMI2 functional homolog-2 (RMIF-2) and RMI1 (RMH-1) have both overlapping and distinct meiotic functions within the BTR complex},
   url = {https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009663},
   volume = {17},
   year = {2021}
}

TY  - JOUR
ID  - 1786884
AU  - Velkova, M. - Silva, Nicola - Dello Stritto, M. R. - Schleiffer, A. - Barraud, P. - Hartl, M. - Jantsch, V.
PY  - 2021
TI  - Caenorhabditis elegans RMI2 functional homolog-2 (RMIF-2) and RMI1 (RMH-1) have both overlapping and distinct meiotic functions within the BTR complex
JF  - PLoS Genetics
VL  - 17
IS  - 7
SP  - 1-32
EP  - 1-32
PB  - Public Library of Science
SN  - 15537404
KW  - Caenorhabditis elegans
KW  - RMIF-2
KW  - RMH-1
KW  - BTR complex
UR  - https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009663
N2  - Author summary Bloom syndrome is caused by mutations in proteins of the BTR complex (consisting of the Bloom helicase, topoisomerase 3, and the RMI1 and RMI2 scaffolding proteins) and the clinical characteristics are growth deficiency, short stature, skin photosensitivity, and increased cancer predisposition. At the cellular level, characteristic features are the presence of increased sister chromatid exchange on chromosomes; unresolved DNA recombination intermediates that eventually cause genome instability; and erroneous DNA repair by heterologous recombination (recombination between non-identical sequences, extremely rare in wild type animals), which can trigger translocations and chromosomal rearrangements. Identification of the Caenorhabditis elegans ortholog of RMI2 (called RMIF-2) allowed us to compare heterologous recombination in the germline of mutants of various BTR complex proteins. The heterologous recombination rate was several fold lower in rmif-2 mutants than in mutants of rmh-1 and him-6 (worm homologs of RMI1 and the Bloom helicase, respectively). Nevertheless, many phenotypic features point at RMIF-2 working together with RMH-1. If these germline functions of RMI2/RMIF-2 are conserved in humans, this might mean that individuals with RMI2 mutations have a lower risk of translocations and genome rearrangements than those with mutations in the other BTR complex genes. Homologous recombination is a high-fidelity repair pathway for DNA double-strand breaks employed during both mitotic and meiotic cell divisions. Such repair can lead to genetic exchange, originating from crossover (CO) generation. In mitosis, COs are suppressed to prevent sister chromatid exchange. Here, the BTR complex, consisting of the Bloom helicase (HIM-6 in worms), topoisomerase 3 (TOP-3), and the RMI1 (RMH-1 and RMH-2) and RMI2 scaffolding proteins, is essential for dismantling joint DNA molecules to form non-crossovers (NCOs) via decatenation. In contrast, in meiosis COs are essential for accurate chromosome segregation and the BTR complex plays distinct roles in CO and NCO generation at different steps in meiotic recombination. RMI2 stabilizes the RMI1 scaffolding protein, and lack of RMI2 in mitosis leads to elevated sister chromatid exchange, as observed upon RMI1 knockdown. However, much less is known about the involvement of RMI2 in meiotic recombination. So far, RMI2 homologs have been found in vertebrates and plants, but not in lower organisms such as Drosophila, yeast, or worms. We report the identification of the Caenorhabditis elegans functional homolog of RMI2, which we named RMIF-2. The protein shows a dynamic localization pattern to recombination foci during meiotic prophase I and concentration into recombination foci is mutually dependent on other BTR complex proteins. Comparative analysis of the rmif-2 and rmh-1 phenotypes revealed numerous commonalities, including in regulating CO formation and directing COs toward chromosome arms. Surprisingly, the prevalence of heterologous recombination was several fold lower in the rmif-2 mutant, suggesting that RMIF-2 may be dispensable or less strictly required for some BTR complex-mediated activities during meiosis.
ER  -

VELKOVA, M., Nicola SILVA, M. R. DELLO STRITTO, A. SCHLEIFFER, P. BARRAUD, M. HARTL and V. JANTSCH. Caenorhabditis elegans RMI2 functional homolog-2 (RMIF-2) and RMI1 (RMH-1) have both overlapping and distinct meiotic functions within the BTR complex. \textit{PLoS Genetics}. San Francisco: Public Library of Science, 2021, vol.~17, No~7, p.~1-32. ISSN~1553-7404. Available from: https://dx.doi.org/10.1371/journal.pgen.1009663.

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