A 2008

Processing of recombination and stalled replication intermediates by MUS81/MMS4 - where proteins MUSt help MUS81

KREJČÍ, Lumír

Basic information

Original name

Processing of recombination and stalled replication intermediates by MUS81/MMS4 - where proteins MUSt help MUS81

Name in Czech

Rozpouštění rekombinačních a replikačních meziproduktů pomoci MUS81/MMS4- kde proteiny musí pomoci MUS81

Edition

Bratislava, Slovakia, 2008

Publisher

Cancer Research Foundation Slovakia

Other information

Language

English

Type of outcome

Audiovizuální tvorba

Field of Study

10600 1.6 Biological sciences

Country of publisher

Slovakia

Confidentiality degree

není předmětem státního či obchodního tajemství

Organization unit

Faculty of Science

Keywords in English

DNA repair; DNA damage; replication; genomic instability

Tags

International impact
Změněno: 31/3/2010 11:40, doc. Mgr. Lumír Krejčí, Ph.D.

Abstract

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. 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.

In Czech

Vliv proteinu Rad54 na biochemickou aktivitu komplexu Mus81/MMS4 při štěpeni rekombinačních a replikačních meziproduktů.

Links

LC06030, research and development project
Name: Biomolekulární centrum
Investor: Ministry of Education, Youth and Sports of the CR, Biomolecular centre
ME 888, research and development project
Name: Srs2 protein a jeho multifunkční úloha při rekombinančních /opravných procesech
Investor: Ministry of Education, Youth and Sports of the CR, Srs2 protein and its multi-functional role in rekombination/repair processes
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