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Mus81 is essential for sister chromatid recombination at broken replication forks

Laura Roseaulin, Yoshiki Yamada, Yasuhiro Tsutsui, Paul Russell, Hiroshi Iwasaki, Benoit Arcangioli

Author Affiliations

  1. Laura Roseaulin1,
  2. Yoshiki Yamada2,
  3. Yasuhiro Tsutsui3,
  4. Paul Russell2,
  5. Hiroshi Iwasaki4 and
  6. Benoit Arcangioli*,1
  1. 1 Genomes and Genetic, Unite de la Dynamique du Génome, URA 2171 du CNRS, Institut Pasteur, Paris, France
  2. 2 Molecular Biology and Cell Biology, The Scripps Research Institute, La Jolla, CA, USA
  3. 3 Division of Mutagenesis, Department of Molecular Biology, National Institute of Genetics, Yata, Mishima, Shizuoka, Japan
  4. 4 International Graduate School of Arts and Sciences, Yokohama City University, Tsurumi‐ku, Yokohama, Japan
  1. *Corresponding author. Genomes and Genetic, Unite de la Dynamique du Génome, URA 2171 du CNRS, Institut Pasteur, 25 rue du Dr Roux, Paris Cedex 75724, France. Tel.: +33 1 4568 8454; Fax: +33 1 4568 8960; E-mail: barcan{at}pasteur.fr
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Abstract

Recombination is essential for the recovery of stalled/collapsed replication forks and therefore for the maintenance of genomic stability. The situation becomes critical when the replication fork collides with an unrepaired single‐strand break and converts it into a one‐ended double‐strand break. We show in fission yeast that a unique broken replication fork requires the homologous recombination (HR) enzymes for cell viability. Two structure‐specific heterodimeric endonucleases participate in two different resolution pathways. Mus81/Eme1 is essential when the sister chromatid is used for repair; conversely, Swi9/Swi10 is essential when an ectopic sequence is used for repair. Consequently, the utilization of these two HR modes of resolution mainly relies on the ratio of unique and repeated sequences present in various eukaryotic genomes. We also provide molecular evidence for sister recombination intermediates. These findings demonstrate that Mus81/Eme1 is the dedicated endonuclease that resolves sister chromatid recombination intermediates during the repair of broken replication forks.

  • Received November 13, 2007.
  • Accepted March 6, 2008.
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