Human RAD51 rapidly forms intrinsically dynamic nucleoprotein
filaments modulated by nucleotide binding state

J 2018

Human RAD51 rapidly forms intrinsically dynamic nucleoprotein filaments modulated by nucleotide binding state

ŠPÍREK, Mário, Jarmila MLČOUŠKOVÁ, Ondrej BELÁŇ, Máté GYIMESI, Gábor M. HARAMI et. al.

Základní údaje

Originální název

Human RAD51 rapidly forms intrinsically dynamic nucleoprotein filaments modulated by nucleotide binding state

Autoři

ŠPÍREK, Mário (703 Slovensko, domácí), Jarmila MLČOUŠKOVÁ (203 Česká republika, domácí), Ondrej BELÁŇ (703 Slovensko, domácí), Máté GYIMESI (348 Maďarsko), Gábor M. HARAMI (348 Maďarsko), Eszter MOLNÁR (348 Maďarsko), Jiří NOVÁČEK (203 Česká republika, domácí), Mihály KOVÁCS (348 Maďarsko) a Lumír KREJČÍ (203 Česká republika, garant, domácí)

Vydání

Nucleic Acids Research, Oxford, Oxford University Press, 2018, 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

Impakt faktor

Impact factor: 11.147

Kód RIV

RIV/00216224:14110/18:00101769

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1093/nar/gky111

UT WoS

000431895800021

Klíčová slova anglicky

RAD51

Štítky

14110513, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 12. 3. 2019 10:37, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

Formation of RAD51 filaments on single-stranded DNA is an essential event during homologous recombination, which is required for homology search, strand exchange and protection of replication forks. Formation of nucleoprotein filaments (NF) is required for development and genomic stability, and its failure is associated with developmental abnormalities and tumorigenesis. Here we describe the structure of the human RAD51 NFs and of its Walker box mutants using electron microscopy. Wild-type RAD51 filaments adopt an 'open' conformation when compared to a 'closed' structure formed by mutants, reflecting alterations in helical pitch. The kinetics of formation/disassembly of RAD51 filaments show rapid and high ssDNA coverage via low cooperativity binding of RAD51 units along the DNA. Subsequently, a series of isomerization or dissociation events mediated by nucleotide binding state creates intrinsically dynamic RAD51 NFs. Our findings highlight important a mechanistic divergence among recombinases from different organisms, in line with the diversity of biological mechanisms of HR initiation and quality control. These data reveal unexpected intrinsic dynamic properties of the RAD51 filament during assembly/disassembly, which may be important for the proper control of homologous recombination.

Návaznosti

GA17-17720S, projekt VaV

Název: Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace

Investor: Grantová agentura ČR, Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace

LM2015043, projekt VaV

Název: Česká infrastruktura pro integrativní strukturní biologii (Akronym: CIISB)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Czech Infrastructure for Integrative Structural Biology

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

ŠPÍREK, Mário, Jarmila MLČOUŠKOVÁ, Ondrej BELÁŇ, Máté GYIMESI, Gábor M. HARAMI, Eszter MOLNÁR, Jiří NOVÁČEK, Mihály KOVÁCS a Lumír KREJČÍ. Human RAD51 rapidly forms intrinsically dynamic nucleoprotein filaments modulated by nucleotide binding state. Nucleic Acids Research. Oxford: Oxford University Press, 2018, roč. 46, č. 8, s. 3967-3980. ISSN 0305-1048. Dostupné z: https://dx.doi.org/10.1093/nar/gky111.

@article{1504904,
   author = {Špírek, Mário and Mlčoušková, Jarmila and Beláň, Ondrej and Gyimesi, Máté and Harami, Gábor M. and Molnár, Eszter and Nováček, Jiří and Kovács, Mihály and Krejčí, Lumír},
   article_location = {Oxford},
   article_number = {8},
   doi = {http://dx.doi.org/10.1093/nar/gky111},
   keywords = {RAD51},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic Acids Research},
   title = {Human RAD51 rapidly forms intrinsically dynamic nucleoprotein filaments modulated by nucleotide binding state},
   volume = {46},
   year = {2018}
}

TY  - JOUR
ID  - 1504904
AU  - Špírek, Mário - Mlčoušková, Jarmila - Beláň, Ondrej - Gyimesi, Máté - Harami, Gábor M. - Molnár, Eszter - Nováček, Jiří - Kovács, Mihály - Krejčí, Lumír
PY  - 2018
TI  - Human RAD51 rapidly forms intrinsically dynamic nucleoprotein filaments modulated by nucleotide binding state
JF  - Nucleic Acids Research
VL  - 46
IS  - 8
SP  - 3967-3980
EP  - 3967-3980
PB  - Oxford University Press
SN  - 03051048
KW  - RAD51
N2  - Formation of RAD51 filaments on single-stranded DNA is an essential event during homologous recombination, which is required for homology search, strand exchange and protection of replication forks. Formation of nucleoprotein filaments (NF) is required for development and genomic stability, and its failure is associated with developmental abnormalities and tumorigenesis. Here we describe the structure of the human RAD51 NFs and of its Walker box mutants using electron microscopy. Wild-type RAD51 filaments adopt an 'open' conformation when compared to a 'closed' structure formed by mutants, reflecting alterations in helical pitch. The kinetics of formation/disassembly of RAD51 filaments show rapid and high ssDNA coverage via low cooperativity binding of RAD51 units along the DNA. Subsequently, a series of isomerization or dissociation events mediated by nucleotide binding state creates intrinsically dynamic RAD51 NFs. Our findings highlight important a mechanistic divergence among recombinases from different organisms, in line with the diversity of biological mechanisms of HR initiation and quality control. These data reveal unexpected intrinsic dynamic properties of the RAD51 filament during assembly/disassembly, which may be important for the proper control of homologous recombination.
ER  -

ŠPÍREK, Mário, Jarmila MLČOUŠKOVÁ, Ondrej BELÁŇ, Máté GYIMESI, Gábor M. HARAMI, Eszter MOLNÁR, Jiří NOVÁČEK, Mihály KOVÁCS a Lumír KREJČÍ. Human RAD51 rapidly forms intrinsically dynamic nucleoprotein filaments modulated by nucleotide binding state. \textit{Nucleic Acids Research}. Oxford: Oxford University Press, 2018, roč.~46, č.~8, s.~3967-3980. ISSN~0305-1048. Dostupné z: https://dx.doi.org/10.1093/nar/gky111.

Podrobný výpis o publikaci