A 2008

Mus81/Mms4 nuclease and cleavage of replication/recombination intermediates

KREJČÍ, Lumír

Basic information

Original name

Mus81/Mms4 nuclease and cleavage of replication/recombination intermediates

Name in Czech

Mus81/Mms4 endonukleáza a štěpení replikačníci/rekombinačních meziproduktů

Edition

Portugalsko, 2008

Publisher

HHMI

Other information

Language

English

Type of outcome

Audiovizuální tvorba

Field of Study

10600 1.6 Biological sciences

Country of publisher

Portugal

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Organization unit

Faculty of Science

Keywords in English

DNA repair; DNA damage; replication; genomic instability

Tags

International impact
Změněno: 31/3/2010 11:37, doc. Mgr. Lumír Krejčí, Ph.D.

Abstract

V originále

DNA replication is typically highly processive mechanism with astonishing precision, despite the fact that it frequently encounters barriers caused by endogenous and exogenous genotoxic agents. It is not surprising that DNA replication does not act alone, but operate in coordination with recombination, and DNA repair processes to overcame such replication obstacles, ensure cellular viability and achieve genomic stability. Several mechanisms by which replication forks can be restarted following arrest have been described with Mus81/Mms4 complex, possessing structure specific endonuclease activity, being one of them. The mus81 mutant shows synthetic interaction with mutations in replication proteins and hypersensitivity genotoxic reagents that in general cause replication fork stalling and collapse. In addition, Mus81 is also known to play role in normal processing of DNA lesion and its inactivation result in elevated levels of genomic instability, elicits checkpoint activation and checkpoint-dependent cell cycle arrest. Our study shows direct association between Rad54 and Mus81 using purified proteins as well as dramatic stimulation of Mus81/Mms4 activity by Rad54 protein on variety of substrates. In addition, we provide evidence that ATP binding and hydrolysis is not required for this stimulation and Rad54 is able to target Mus81/Mms4 complex to its substrates. We propose that Rad54 together with Mus81/Mms4 protein is involved in processing DNA substrates that are intermediates arising during DNA replication and recombination.

In Czech

Charakterizace strukturně-specifické nukleázy Mus81/MMS4 při rozpouštění 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