Functional overlap between the structure-specific nucleases Yen1 and Mus81-Mms4 for DNA-damage repair in S. cerevisiae.

Blanco, Miguel G, Matos, Joao, Rass, Ulrich, Ip, Stephen C Y and West, Stephen C (2010) Functional overlap between the structure-specific nucleases Yen1 and Mus81-Mms4 for DNA-damage repair in S. cerevisiae. DNA repair, 9 (4). pp. 394-402. ISSN 1568-7864

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Abstract

In eukaryotic cells, multiple DNA repair mechanisms respond to a wide variety of DNA lesions. Homologous recombination-dependent repair provides a pathway for dealing with DNA double-strand breaks and replication fork demise. A key step in this process is the resolution of recombination intermediates such as Holliday junctions (HJs). Recently, nucleases from yeast (Yen1) and human cells (GEN1) were identified that can resolve HJ intermediates, in a manner analogous to the E. coli HJ resolvase RuvC. Here, we have analyzed the role of Yen1 in DNA repair in S. cerevisiae, and show that while yen1Delta mutants are repair-proficient, yen1Delta mus81Delta double mutants are exquisitely sensitive to a variety of DNA-damaging agents that disturb replication fork progression. This phenotype is dependent upon RAD52, indicating that toxic recombination intermediates accumulate in the absence of Yen1 and Mus81. After MMS treatment, yen1Delta mus81Delta double mutants arrest with a G2 DNA content and unsegregated chromosomes. These findings indicate that Yen1 can act upon recombination/repair intermediates that arise in MUS81-defective cells following replication fork damage.

Item Type: Article
Keywords: DNA repair, homologous recombination, Holliday junction resolution, structure-specific nucleases, Yen1, Mus81
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups: Genome Damage and Stability Centre
Subjects: Q Science > Q Science (General) > Q0179.9 Research
Q Science > Q Science (General)
Depositing User: Ulrich Rass
Date Deposited: 26 Sep 2018 07:52
Last Modified: 02 Nov 2018 16:09
URI: http://srodev.sussex.ac.uk/id/eprint/79009
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