Genetics, Vol. 158, 95-107, May 2001, Copyright © 2001

Saccharomyces cerevisiae SMT4 Encodes an Evolutionarily Conserved Protease With a Role in Chromosome Condensation Regulation

Alexander V. Strunnikova, L. Aravindb, and Eugene V. Kooninb
a National Institute of Child Health and Human Development, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20892
b National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20892

Corresponding author: Alexander V. Strunnikov, NIH, NICHD, LGRD, 18T Library Dr., Rm. 106, Bethesda, MD 20892., strunnik{at}box-s.nih.gov (E-mail)

Communicating editor: S. HENIKOFF

In a search for regulatory genes affecting the targeting of the condensin complex to chromatin in Saccharomyces cerevisiae, we identified a member of the adenovirus protease family, SMT4. SMT4 overexpression suppresses the temperature-sensitive conditional lethal phenotype of smc2-6, but not smc2-8 or smc4-1. A disruption allele of SMT4 has a prominent chromosome phenotype: impaired targeting of Smc4p-GFP to rDNA chromatin. Site-specific mutagenesis of the predicted protease active site cysteine and histidine residues of Smt4p abolishes the SMT4 function in vivo. The previously uncharacterized SIZ1 (SAP and Miz) gene, which encodes a protein containing a predicted DNA-binding SAP module and a Miz finger, is identified as a bypass suppressor of the growth defect associated with the SMT4 disruption. The SIZ1 gene disruption is synthetically lethal with the SIZ2 deletion. We propose that SMT4, SIZ1, and SIZ2 are involved in a novel pathway of chromosome maintenance.





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