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KREJČÍ, Lumír, Stephen VAN KOMEN, Ying LI, Jane VILLEMAIN, Sredhar REDDY, Hannah KLEIN, Tom ELLENBERGER a Patrick SUNG. DNA helicase Srs2 disrupts the Rad51 presynaptic filament. Online. Nature. Lodon, UK: Nature Publishing Group, 2003, roč. 423, č. 6937, s. 305-9, 4 s. ISSN 0028-0836. [citováno 2024-04-23]

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Základní údaje
Originální název	DNA helicase Srs2 disrupts the Rad51 presynaptic filament.
Název česky	DNA helicase Srs2 disrupts the Rad51 presynaptic filament.
Autoři	KREJČÍ, Lumír (203 Česká republika, garant), Stephen VAN KOMEN (840 Spojené státy), Ying LI (840 Spojené státy), Jane VILLEMAIN (840 Spojené státy), Sredhar REDDY (356 Indie), Hannah KLEIN (840 Spojené státy), Tom ELLENBERGER (840 Spojené státy) a Patrick SUNG (840 Spojené státy)
Vydání	Nature, Lodon, UK, Nature Publishing Group, 2003, 0028-0836.

Další údaje
Originální jazyk	angličtina
Typ výsledku	Článek v odborném periodiku
Obor	10600 1.6 Biological sciences
Stát vydavatele	Spojené státy
Utajení	není předmětem státního či obchodního tajemství
Impakt faktor	Impact factor: 30.979
Organizační jednotka	Přírodovědecká fakulta
Klíčová slova anglicky	recombination; repair; Srs2;Rad51
Štítky	Rad51, recombination, repair, Srs2
Příznaky	Mezinárodní význam, Recenzováno
Změnil	Změnil: doc. Mgr. Lumír Krejčí, Ph.D., učo 18098. Změněno: 15. 5. 2009 22:59.

Anotace
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.

Anotace

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.

Anotace česky
Srs2 a jeho anti-rekombinační aktivita