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.

Basic information

Original name

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

Authors

ŠPÍREK, Mário (703 Slovakia, belonging to the institution), Jarmila MLČOUŠKOVÁ (203 Czech Republic, belonging to the institution), Ondrej BELÁŇ (703 Slovakia, belonging to the institution), Máté GYIMESI (348 Hungary), Gábor M. HARAMI (348 Hungary), Eszter MOLNÁR (348 Hungary), Jiří NOVÁČEK (203 Czech Republic, belonging to the institution), Mihály KOVÁCS (348 Hungary) and Lumír KREJČÍ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Nucleic Acids Research, Oxford, Oxford University Press, 2018, 0305-1048

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

Impact factor

Impact factor: 11.147

RIV identification code

RIV/00216224:14110/18:00101769

Organization unit

Faculty of Medicine

DOI

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

UT WoS

000431895800021

Keywords in English

RAD51

Abstract

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.

Links

GA17-17720S, research and development project

Name: Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace

Investor: Czech Science Foundation

LM2015043, research and development project

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

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

206292/E/17/Z, interní kód MU

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

Investor: Wellcome Trust

Citovat

ŠPÍREK, Mário, Jarmila MLČOUŠKOVÁ, Ondrej BELÁŇ, Máté GYIMESI, Gábor M. HARAMI, Eszter MOLNÁR, Jiří NOVÁČEK, Mihály KOVÁCS and Lumír KREJČÍ. Human RAD51 rapidly forms intrinsically dynamic nucleoprotein filaments modulated by nucleotide binding state. Nucleic Acids Research. Oxford: Oxford University Press, 2018, vol. 46, No 8, p. 3967-3980. ISSN 0305-1048. Available from: 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 and Lumír KREJČÍ. Human RAD51 rapidly forms intrinsically dynamic nucleoprotein filaments modulated by nucleotide binding state. \textit{Nucleic Acids Research}. Oxford: Oxford University Press, 2018, vol.~46, No~8, p.~3967-3980. ISSN~0305-1048. Available from: https://dx.doi.org/10.1093/nar/gky111.

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