The role of bivalent ions in the regulation of D-loop extension
mediated by DMC1 during meiotic recombination

J 2022

The role of bivalent ions in the regulation of D-loop extension mediated by DMC1 during meiotic recombination

ALTMANNOVÁ, Veronika, Mário ŠPÍREK, Lucija ORLIC, Atis JEKABSONS, Tereza CLARENCE et. al.

Basic information

Original name

The role of bivalent ions in the regulation of D-loop extension mediated by DMC1 during meiotic recombination

Authors

ALTMANNOVÁ, Veronika (203 Czech Republic, belonging to the institution), Mário ŠPÍREK (703 Slovakia, belonging to the institution), Lucija ORLIC, Atis JEKABSONS (428 Latvia, belonging to the institution), Tereza CLARENCE, Adrian HENGGELER, Jarmila MLCOUSKOVA, Raphael A G CHALEIL, Joao MATOS and Lumír KREJČÍ (203 Czech Republic, guarantor, belonging to the institution)

Edition

iSCIENCE, CAMBRIDGE, CELL PRESS, 2022, 2589-0042

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.800

RIV identification code

RIV/00216224:14110/22:00128839

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.isci.2022.105439

UT WoS

000923030100007

Keywords in English

DMC1; meiotic recombination; D-loop extension; bivalent ions

Abstract

V originále

During meiosis, programmed DNA double-strand breaks (DSBs) are repaired by homologous recombination. DMC1, a conserved recombinase, plays a central role in this process. DMC1 promotes DNA strand exchange between homologous chromosomes, thus creating the physical linkage between them. Its function is regulated not only by several accessory proteins but also by bivalent ions. Here, we show that whereas calcium ions in the presence of ATP cause a conformational change within DMC1, stimulating its DNA binding and D-loop formation, they inhibit the extension of the invading strand within the D-loop. Based on structural studies, we have generated mutants of two highly conserved amino acids - E162 and D317 - in human DMC1, which are deficient in calcium regulation. In vivo studies of their yeast homologues further showed that they exhibit severe defects in meiosis, thus emphasizing the importance of calcium ions in the regulation of DMC1 function and meiotic recombination.

Links

EF16_025/0007381, research and development project

Name: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou

GX21-22593X, research and development project

Name: Identifikace a charakterizace proteinů zahrnutých v metabolismu G-kvadruplexů a R-smyček a jejich vztah k replikaci DNA

LM2018127, research and development project

Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)

Investor: Ministry of Education, Youth and Sports of the CR

LM2018140, research and development project

Name: e-Infrastruktura CZ (Acronym: e-INFRA CZ)

Investor: Ministry of Education, Youth and Sports of the CR

MUNI/G/1594/2019, interní kód MU

Name: RecQ4 – a protein hub required for proper replication and recombination and its implications in Rothmund-Thomson Syndrome

Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects

206292/E/17/Z, interní kód MU

Name: Mechanics and execution of homologous recombination - biophysics to the organism

Investor: Wellcome Trust

Citovat

ALTMANNOVÁ, Veronika, Mário ŠPÍREK, Lucija ORLIC, Atis JEKABSONS, Tereza CLARENCE, Adrian HENGGELER, Jarmila MLCOUSKOVA, Raphael A G CHALEIL, Joao MATOS and Lumír KREJČÍ. The role of bivalent ions in the regulation of D-loop extension mediated by DMC1 during meiotic recombination. iSCIENCE. CAMBRIDGE: CELL PRESS, 2022, vol. 25, No 11, p. 1-26. ISSN 2589-0042. Available from: https://dx.doi.org/10.1016/j.isci.2022.105439.

@article{2266078,
   author = {Altmannová, Veronika and Špírek, Mário and Orlic, Lucija and Jekabsons, Atis and Clarence, Tereza and Henggeler, Adrian and Mlcouskova, Jarmila and Chaleil, Raphael A G and Matos, Joao and Krejčí, Lumír},
   article_location = {CAMBRIDGE},
   article_number = {11},
   doi = {http://dx.doi.org/10.1016/j.isci.2022.105439},
   keywords = {DMC1; meiotic recombination; D-loop extension; bivalent ions},
   language = {eng},
   issn = {2589-0042},
   journal = {iSCIENCE},
   title = {The role of bivalent ions in the regulation of D-loop extension mediated by DMC1 during meiotic recombination},
   url = {https://www.cell.com/iscience/fulltext/S2589-0042(22)01711-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2589004222017114%3Fshowall%3Dtrue},
   volume = {25},
   year = {2022}
}

TY  - JOUR
ID  - 2266078
AU  - Altmannová, Veronika - Špírek, Mário - Orlic, Lucija - Jekabsons, Atis - Clarence, Tereza - Henggeler, Adrian - Mlcouskova, Jarmila - Chaleil, Raphael A G - Matos, Joao - Krejčí, Lumír
PY  - 2022
TI  - The role of bivalent ions in the regulation of D-loop extension mediated by DMC1 during meiotic recombination
JF  - iSCIENCE
VL  - 25
IS  - 11
SP  - 1-26
EP  - 1-26
PB  - CELL PRESS
SN  - 25890042
KW  - DMC1
KW  - meiotic recombination
KW  - D-loop extension
KW  - bivalent ions
UR  - https://www.cell.com/iscience/fulltext/S2589-0042(22)01711-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2589004222017114%3Fshowall%3Dtrue
N2  - During meiosis, programmed DNA double-strand breaks (DSBs) are repaired by homologous recombination. DMC1, a conserved recombinase, plays a central role in this process. DMC1 promotes DNA strand exchange between homologous chromosomes, thus creating the physical linkage between them. Its function is regulated not only by several accessory proteins but also by bivalent ions. Here, we show that whereas calcium ions in the presence of ATP cause a conformational change within DMC1, stimulating its DNA binding and D-loop formation, they inhibit the extension of the invading strand within the D-loop. Based on structural studies, we have generated mutants of two highly conserved amino acids - E162 and D317 - in human DMC1, which are deficient in calcium regulation. In vivo studies of their yeast homologues further showed that they exhibit severe defects in meiosis, thus emphasizing the importance of calcium ions in the regulation of DMC1 function and meiotic recombination.
ER  -

ALTMANNOVÁ, Veronika, Mário ŠPÍREK, Lucija ORLIC, Atis JEKABSONS, Tereza CLARENCE, Adrian HENGGELER, Jarmila MLCOUSKOVA, Raphael A G CHALEIL, Joao MATOS and Lumír KREJČÍ. The role of bivalent ions in the regulation of D-loop extension mediated by DMC1 during meiotic recombination. \textit{iSCIENCE}. CAMBRIDGE: CELL PRESS, 2022, vol.~25, No~11, p.~1-26. ISSN~2589-0042. Available from: https://dx.doi.org/10.1016/j.isci.2022.105439.

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