2008
Stimulation of Mus81-Mms4 activity by Rad54
KREJČÍ, LumírZákladní údaje
Originální název
Stimulation of Mus81-Mms4 activity by Rad54
Název česky
Stimulace Mus81/MMS4 endonukleázy Rad54 proteinem
Autoři
Vydání
London, Wellcome Trust, 2008
Nakladatel
Wellcome Trust
Další údaje
Jazyk
angličtina
Typ výsledku
Audiovizuální tvorba
Obor
10600 1.6 Biological sciences
Stát vydavatele
Velká Británie a Severní Irsko
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Organizační jednotka
Přírodovědecká fakulta
Klíčová slova anglicky
DNA repair; DNA damage; replication; genomic instability
Štítky
Příznaky
Mezinárodní význam
Změněno: 31. 3. 2010 11:45, doc. Mgr. Lumír Krejčí, Ph.D.
V originále
The Saccharomyces cerevisae Mus81-Mms4 protein complex, a DNA structure-specific endonuclease, helps preserve genomic integrity by resolving pathological DNA structures that arise from damaged or aborted replication forks and may also play a role in the resolution of DNA intermediates arising through homologous recombination. Previous yeast two hybrid studies have found an interaction of the Mus81 protein with Rad54, a Swi2/Snf2-like factor that serves multiple roles in homologous recombination processes, but the functional significance of this novel interaction remains unknown. Using highly purified S. cerevisiae proteins, we show that Rad54 strongly stimulates the Mus81-Mms4 nuclease activity on a broad range of DNA substrates. This nuclease enhancement does not require ATP binding nor its hydrolysis by Rad54. We present evidence that Rad54 acts by targeting Mus81-Mms4 complex to its DNA substrates. The association of Rad54 with Mus81-Mms4 complex appears to be species specific, as suggested by the limited ability of human Rad54 protein to stimulate the Mus81-Mms4 complex or of the yeast Rad54 counterpart to enhance the nuclease activity of the human equivalent Mus81-Eme1. We propose that Mus81-Mms4 together with Rad54 efficiently process perturbed replication forks to promote recovery and may constitute an alternative mechanism to resolution/dissolution of the recombination intermediates by Sgs1-Top3. These findings provide functional insights into the biological importance of the higher order complex of Mus81-Mms4 or its orthologue with Rad54.
Česky
The Saccharomyces cerevisae Mus81-Mms4 protein complex, a DNA structure-specific endonuclease, helps preserve genomic integrity by resolving pathological DNA structures that arise from damaged or aborted replication forks and may also play a role in the resolution of DNA intermediates arising through homologous recombination. Previous yeast two hybrid studies have found an interaction of the Mus81 protein with Rad54, a Swi2/Snf2-like factor that serves multiple roles in homologous recombination processes, but the functional significance of this novel interaction remains unknown. Using highly purified S. cerevisiae proteins, we show that Rad54 strongly stimulates the Mus81-Mms4 nuclease activity on a broad range of DNA substrates. This nuclease enhancement does not require ATP binding nor its hydrolysis by Rad54. We present evidence that Rad54 acts by targeting Mus81-Mms4 complex to its DNA substrates. The association of Rad54 with Mus81-Mms4 complex appears to be species specific, as suggested by the limited ability of human Rad54 protein to stimulate the Mus81-Mms4 complex or of the yeast Rad54 counterpart to enhance the nuclease activity of the human equivalent Mus81-Eme1. We propose that Mus81-Mms4 together with Rad54 efficiently process perturbed replication forks to promote recovery and may constitute an alternative mechanism to resolution/dissolution of the recombination intermediates by Sgs1-Top3. These findings provide functional insights into the biological importance of the higher order complex of Mus81-Mms4 or its orthologue with Rad54.
Návaznosti
| LC06030, projekt VaV |
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| ME 888, projekt VaV |
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| MSM0021622413, záměr |
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