TY - JOUR
T1 - The role of bivalent ions in the regulation of D-loop extension mediated by DMC1 during meiotic recombination
AU - Altmannova, Veronika
AU - Spirek, Mario
AU - Orlic, Lucija
AU - Jēkabsons, Atis
AU - Clarence, Tereza
AU - Henggeler, Adrian
AU - Mlcouskova, Jarmila
AU - Chaleil, Raphaël A.G.
AU - Matos, Joao
AU - Krejci, Lumir
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/11/18
Y1 - 2022/11/18
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.
AB - 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.
KW - Cell biology
KW - Structural biology
UR - http://www.scopus.com/inward/record.url?scp=85141242414&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2022.105439
DO - 10.1016/j.isci.2022.105439
M3 - Article
AN - SCOPUS:85141242414
SN - 2589-0042
VL - 25
JO - Iscience
JF - Iscience
IS - 11
M1 - 105439
ER -