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PMID: 17502373 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Fission yeast Rnf4 homologs are required for DNA repair.

The Journal of biological chemistry ·Vol. 282 ·No. 28 ·2007-07-13 ·Pages 20388-94

Kosoy A, Calonge TM, Outwin EA, O'Connell MJ

Abstract

We describe two RING finger proteins in the fission yeast Schizosaccharomyces pombe, Rfp1 and Rfp2. We show that these proteins function redundantly in DNA repair. Rfp1 was isolated as a Chk1-interacting protein in a two-hybrid screen and has high amino acid sequence similarity to Rfp2. Deletion of either gene does not cause a phenotype, but a double deletion (rfp1Deltarfp2Delta) showed poor viability and defects in cell cycle progression. These cells are also sensitive to DNA-damaging agents, although they maintained normal checkpoint signaling to Chk1. Rfp1 and Rfp2 are most closely related to human Rnf4, and we showed that Rnf4 can substitute functionally for Rfp1 and/or Rfp2. The double mutants also showed significantly increased levels of protein SUMOylation, and we identified an S. pombe Ulp2/Smt4 homolog that, when overexpressed, reduced SUMO levels and suppressed the DNA damage sensitivity of rfp1Delta rfp2Delta cells.

MeSH Terms
Cell Cycle/physiology Checkpoint Kinase 1 DNA Repair/physiology DNA, Fungal/genetics,metabolism Gene Deletion Humans Nuclear Proteins/genetics,metabolism Protein Kinases/genetics,metabolism Protein Processing, Post-Translational Schizosaccharomyces/genetics,metabolism Schizosaccharomyces pombe Proteins/genetics,metabolism Sequence Homology, Amino Acid Small Ubiquitin-Related Modifier Proteins/genetics,metabolism Transcription Factors/genetics,metabolism
Chemicals
DNA, Fungal Nuclear Proteins RNF4 protein, human Rfp1 protein, S pombe Rfp2 protein, S pombe Schizosaccharomyces pombe Proteins Small Ubiquitin-Related Modifier Proteins Transcription Factors Protein Kinases CHEK1 protein, human Checkpoint Kinase 1 Chk1 protein, S pombe
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kosoy Ana
Department of Oncological Sciences, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
Calonge Teresa M
Outwin Emily A
O'Connell Matthew J
Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
Published
2007-07-13
Epub
2007-00-14
Pages
20388-94
Language
English
Region
United States
NLM ID
2985121R
Subset
IM
Grants
NCI NIH HHS · CA 100076 · United States
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