Role of interaction od Rad54 with Mus81/MMS4 during DNA repair

MATULOVÁ, Petra. Role of interaction od Rad54 with Mus81/MMS4 during DNA repair. 2008.

Basic information

• Original name: Role of interaction od Rad54 with Mus81/MMS4 during DNA repair
• Name in Czech: Role Rad54 a Mus81/MMS4 během opravy DNA
• Authors: MATULOVÁ, Petra (203 Czech Republic, guarantor).
• Edition: 2008.

Other information

• Original language: English
• Type of outcome: Audiovisual works
• Field of Study: 10600 1.6 Biological sciences
• Country of publisher: Czech Republic
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• RIV identification code: RIV/00216224:14310/08:00026762
• Organization unit: Faculty of Science
• Keywords in English: DNA repair; homologous recombination; nuclease activity; MUS81; Rad54
• Tags: DNA repair, HOMOLOGOUS RECOMBINATION, MUS81, nuclease activity, Rad54
• Tags: International impact

Abstract

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. Here, 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.

Abstract (in Czech)

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. Here, 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

Links

• MSM 143100005, plan (intention): Name: Strukturně-funkční vztahy biomolekul a jejich role v metabolismu

Investor: Ministry of Education, Youth and Sports of the CR, Biomolecular Structure-function Relationships and their role in the Metabolism

• MSM0021622413, plan (intention): Name: Proteiny v metabolismu a při interakci organismů s prostředím

Investor: Ministry of Education, Youth and Sports of the CR, Proteins in metabolism and interaction of organisms with the environment