Physical interaction with Spo11 mediates the localisation of
Mre11 to chromatin in meiosis and promotes its nuclease
activity

J 2024

Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity

AITHAL, Rakesh, Kuldeep NANGALIA, Mário ŠPÍREK, Doris CHEN, Franz KLEIN et. al.

Základní údaje

Originální název

Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity

Autoři

AITHAL, Rakesh (356 Indie, domácí), Kuldeep NANGALIA, Mário ŠPÍREK (703 Slovensko, domácí), Doris CHEN, Franz KLEIN a Lumír KREJČÍ (203 Česká republika, domácí)

Vydání

Nucleic acids research, Oxford, Oxford University Press, 2024, 0305-1048

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 14.900 v roce 2022

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1093/nar/gkae111

UT WoS

001173092200001

Klíčová slova anglicky

Spo11; Mre11; Meiosis; Chromatin localization; Nuclease activity

Štítky

14110513, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 11. 2024 14:47, Mgr. Tereza Miškechová

Anotace

V originále

Meiotic recombination is of central importance for the proper segregation of homologous chromosomes, but also for creating genetic diversity. It is initiated by the formation of double-strand breaks (DSBs) in DNA catalysed by evolutionarily conserved Spo11, together with additional protein partners. Difficulties in purifying the Spo11 protein have limited the characterization of its biochemical properties and of its interactions with other DSB proteins. In this study, we have purified fragments of Spo11 and show for the first time that Spo11 can physically interact with Mre11 and modulates its DNA binding, bridging, and nuclease activities. The interaction of Mre11 with Spo11 requires its far C-terminal region, which is in line with the severe meiotic phenotypes of various mre11 mutations located at the C-terminus. Moreover, calibrated ChIP for Mre11 shows that Spo11 promotes Mre11 recruitment to chromatin, independent of DSB formation. A mutant deficient in Spo11 interaction severely reduces the association of Mre11 with meiotic chromatin. Consistent with the reduction of Mre11 foci in this mutant, it strongly impedes DSB formation, leading to spore death. Our data provide evidence that physical interaction between Spo11 and Mre11, together with end-bridging, promote normal recruitment of Mre11 to hotspots and DSB formation.

Návaznosti

EF16_025/0007381, projekt VaV

Název: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou

GX21-22593X, projekt VaV

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

206292/E/17/Z, interní kód MU

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

Investor: Wellcome Trust, Mechanics and execution of homologous recombination - biophysics to the organism

Citovat

AITHAL, Rakesh, Kuldeep NANGALIA, Mário ŠPÍREK, Doris CHEN, Franz KLEIN a Lumír KREJČÍ. Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity. Nucleic acids research. Oxford: Oxford University Press, 2024, roč. 52, č. 8, s. 4328-4343. ISSN 0305-1048. Dostupné z: https://dx.doi.org/10.1093/nar/gkae111.

@article{2387600,
   author = {Aithal, Rakesh and Nangalia, Kuldeep and Špírek, Mário and Chen, Doris and Klein, Franz and Krejčí, Lumír},
   article_location = {Oxford},
   article_number = {8},
   doi = {http://dx.doi.org/10.1093/nar/gkae111},
   keywords = {Spo11; Mre11; Meiosis; Chromatin localization; Nuclease activity},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic acids research},
   title = {Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity},
   url = {https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkae111/7614131?login=true},
   volume = {52},
   year = {2024}
}

TY  - JOUR
ID  - 2387600
AU  - Aithal, Rakesh - Nangalia, Kuldeep - Špírek, Mário - Chen, Doris - Klein, Franz - Krejčí, Lumír
PY  - 2024
TI  - Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity
JF  - Nucleic acids research
VL  - 52
IS  - 8
SP  - 4328-4343
EP  - 4328-4343
PB  - Oxford University Press
SN  - 03051048
KW  - Spo11
KW  - Mre11
KW  - Meiosis
KW  - Chromatin localization
KW  - Nuclease activity
UR  - https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkae111/7614131?login=true
N2  - Meiotic recombination is of central importance for the proper segregation of homologous chromosomes, but also for creating genetic diversity. It is initiated by the formation of double-strand breaks (DSBs) in DNA catalysed by evolutionarily conserved Spo11, together with additional protein partners. Difficulties in purifying the Spo11 protein have limited the characterization of its biochemical properties and of its interactions with other DSB proteins. In this study, we have purified fragments of Spo11 and show for the first time that Spo11 can physically interact with Mre11 and modulates its DNA binding, bridging, and nuclease activities. The interaction of Mre11 with Spo11 requires its far C-terminal region, which is in line with the severe meiotic phenotypes of various mre11 mutations located at the C-terminus. Moreover, calibrated ChIP for Mre11 shows that Spo11 promotes Mre11 recruitment to chromatin, independent of DSB formation. A mutant deficient in Spo11 interaction severely reduces the association of Mre11 with meiotic chromatin. Consistent with the reduction of Mre11 foci in this mutant, it strongly impedes DSB formation, leading to spore death. Our data provide evidence that physical interaction between Spo11 and Mre11, together with end-bridging, promote normal recruitment of Mre11 to hotspots and DSB formation.
ER  -

AITHAL, Rakesh, Kuldeep NANGALIA, Mário ŠPÍREK, Doris CHEN, Franz KLEIN a Lumír KREJČÍ. Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity. \textit{Nucleic acids research}. Oxford: Oxford University Press, 2024, roč.~52, č.~8, s.~4328-4343. ISSN~0305-1048. Dostupné z: https://dx.doi.org/10.1093/nar/gkae111.

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