DNA helicase Srs2 disrupts the Rad51 presynaptic filament.

J 2003

DNA helicase Srs2 disrupts the Rad51 presynaptic filament.

KREJČÍ, Lumír, Stephen VAN KOMEN, Ying LI, Jane VILLEMAIN, Sredhar REDDY et. al.

Basic information

Original name

DNA helicase Srs2 disrupts the Rad51 presynaptic filament.

Name in Czech

DNA helicase Srs2 disrupts the Rad51 presynaptic filament.

Authors

KREJČÍ, Lumír (203 Czech Republic, guarantor), Stephen VAN KOMEN (840 United States of America), Ying LI (840 United States of America), Jane VILLEMAIN (840 United States of America), Sredhar REDDY (356 India), Hannah KLEIN (840 United States of America), Tom ELLENBERGER (840 United States of America) and Patrick SUNG (840 United States of America)

Edition

Nature, Lodon, UK, Nature Publishing Group, 2003, 0028-0836

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 30.979

Organization unit

Faculty of Science

Keywords in English

recombination; repair; Srs2;Rad51

Abstract

ORIG CZ

V originále

Mutations in the Saccharomyces cerevisiae gene SRS2 result in the yeast's sensitivity to genotoxic agents, failure to recover or adapt from DNA damage checkpoint-mediated cell cycle arrest, slow growth, chromosome loss, and hyper-recombination. Furthermore, double mutant strains, with mutations in DNA helicase genes SRS2 and SGS1, show low viability that can be overcome by inactivating recombination, implying that untimely recombination is the cause of growth impairment. Here we clarify the role of SRS2 in recombination modulation by purifying its encoded product and examining its interactions with the Rad51 recombinase. Srs2 has a robust ATPase activity that is dependent on single-stranded DNA (ssDNA) and binds Rad51, but the addition of a catalytic quantity of Srs2 to Rad51-mediated recombination reactions causes severe inhibition of these reactions. We show that Srs2 acts by dislodging Rad51 from ssDNA. Thus, the attenuation of recombination efficiency by Srs2 stems primarily from its ability to dismantle the Rad51 presynaptic filament efficiently. Our findings have implications for the basis of Bloom's and Werner's syndromes, which are caused by mutations in DNA helicases and are characterized by increased frequencies of recombination and a predisposition to cancers and accelerated ageing.

In Czech

Srs2 a jeho anti-rekombinační aktivita

Citovat

KREJČÍ, Lumír, Stephen VAN KOMEN, Ying LI, Jane VILLEMAIN, Sredhar REDDY, Hannah KLEIN, Tom ELLENBERGER and Patrick SUNG. DNA helicase Srs2 disrupts the Rad51 presynaptic filament. Nature. Lodon, UK: Nature Publishing Group, 2003, vol. 423, No 6937, p. 305-9, 4 pp. ISSN 0028-0836.

@article{708586,
   author = {Krejčí, Lumír and Van Komen, Stephen and Li, Ying and Villemain, Jane and Reddy, Sredhar and Klein, Hannah and Ellenberger, Tom and Sung, Patrick},
   article_location = {Lodon, UK},
   article_number = {6937},
   keywords = {recombination; repair; Srs2;Rad51},
   language = {eng},
   issn = {0028-0836},
   journal = {Nature},
   title = {DNA helicase Srs2 disrupts the Rad51 presynaptic filament.},
   volume = {423},
   year = {2003}
}

TY  - JOUR
ID  - 708586
AU  - Krejčí, Lumír - Van Komen, Stephen - Li, Ying - Villemain, Jane - Reddy, Sredhar - Klein, Hannah - Ellenberger, Tom - Sung, Patrick
PY  - 2003
TI  - DNA helicase Srs2 disrupts the Rad51 presynaptic filament.
JF  - Nature
VL  - 423
IS  - 6937
SP  - 305-9
EP  - 305-9
PB  - Nature Publishing Group
SN  - 00280836
KW  - recombination
KW  - repair
KW  - Srs2;Rad51
N2  - Mutations in the Saccharomyces cerevisiae gene SRS2 result in the yeast's sensitivity to genotoxic agents, failure to recover or adapt from DNA damage checkpoint-mediated cell cycle arrest, slow growth, chromosome loss, and hyper-recombination. Furthermore, double mutant strains, with mutations in DNA helicase genes SRS2 and SGS1, show low viability that can be overcome by inactivating recombination, implying that untimely recombination is the cause of growth impairment. Here we clarify the role of SRS2 in recombination modulation by purifying its encoded product and examining its interactions with the Rad51 recombinase. Srs2 has a robust ATPase activity that is dependent on single-stranded DNA (ssDNA) and binds Rad51, but the addition of a catalytic quantity of Srs2 to Rad51-mediated recombination reactions causes severe inhibition of these reactions. We show that Srs2 acts by dislodging Rad51 from ssDNA. Thus, the attenuation of recombination efficiency by Srs2 stems primarily from its ability to dismantle the Rad51 presynaptic filament efficiently. Our findings have implications for the basis of Bloom's and Werner's syndromes, which are caused by mutations in DNA helicases and are characterized by increased frequencies of recombination and a predisposition to cancers and accelerated ageing.
ER  -

KREJČÍ, Lumír, Stephen VAN KOMEN, Ying LI, Jane VILLEMAIN, Sredhar REDDY, Hannah KLEIN, Tom ELLENBERGER and Patrick SUNG. DNA helicase Srs2 disrupts the Rad51 presynaptic filament. \textit{Nature}. Lodon, UK: Nature Publishing Group, 2003, vol.~423, No~6937, p.~305-9, 4 pp. ISSN~0028-0836.

Detailed Information on Publication Record