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Originally published as Genetics Published Articles Ahead of Print on August 30, 2008.
Genetics, Vol. 180, 41-50, September 2008, Copyright © 2008
doi:10.1534/genetics.107.086249
A SUMO-Like Domain Protein, Esc2, Is Required for Genome Integrity and Sister Chromatid Cohesion in Saccharomyces cerevisiae
Tomoko Ohya*,
Hirokazu Arai*,
Yoshino Kubota*,
Hideo Shinagawa*,
and
Takashi Hishida*,1
* Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871 Japan and
BioAcademia, Ibaraki, Osaka, 565-0085 Japan
1 Corresponding author: Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
E-mail: hishida{at}biken.osaka-u.ac.jp
The ESC2 gene encodes a protein with two tandem C-terminal SUMO-like domains and is conserved from yeasts to humans. Previous studies have implicated Esc2 in gene silencing. Here, we explore the functional significance of SUMO-like domains and describe a novel role for Esc2 in promoting genome integrity during DNA replication. This study shows that esc2
cells are modestly sensitive to hydroxyurea (HU) and defective in sister chromatid cohesion and have a reduced life span, and these effects are enhanced by deletion of the RRM3 gene that is a Pif1-like DNA helicase. esc2
rrm3
cells also have a severe growth defect and accumulate DNA damage in late S/G2. In contrast, esc2
does not enhance the HU sensitivity or sister chromatid cohesion defect in mrc1
cells, but rather partially suppresses both phenotypes. We also show that deletion of both Esc2 SUMO-like domains destabilizes Esc2 protein and functionally inactivates Esc2, but this phenotype is suppressed by an Esc2 variant with an authentic SUMO domain. These results suggest that Esc2 is functionally equivalent to a stable SUMO fusion protein and plays important roles in facilitating DNA replication fork progression and sister chromatid cohesion that would otherwise impede the replication fork in rrm3
cells.
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Genetics 2008 180: NP.