Mitotic Chromosome Transmission Fidelity Mutants in Saccharomyces cerevisiae

INVESTIGATIONS

Mitotic Chromosome Transmission Fidelity Mutants in Saccharomyces cerevisiae

F. Spencer, S. L. Gerring, C. Connelly and P. Hieter
Department of Molecular Biology and Genetics, Johns Hopkins Medical School, Baltimore, Maryland 21205

We have isolated 136 independent mutations in haploid yeast strains that exhibit decreased chromosome transmission fidelity in mitosis. Eighty-five percent of the mutations are recessive and 15% are partially dominant. Complementation analysis between MATa and MAT{alpha} isolates identifies 11 chromosome transmission fidelity (CTF) complementation groups, the largest of which is identical to CHL1. For 49 independent mutations, no corresponding allele has been recovered in the opposite mating type. The initial screen monitored the stability of a centromere-linked color marker on a nonessential yeast chromosome fragment; the mitotic inheritance of natural yeast chromosome III is also affected by the ctf mutations. Of the 136 isolates identified, seven were inviable at 37{deg} and five were inviable at 11{deg}. In all cases tested, these temperature conditional lethalities cosegregated with the chromosome instability phenotype. Five additional complementation groups (ctf12 through ctf16) have been defined by complementation analysis of the mutations causing inviability at 37{deg}. Twenty-three of the 136 isolates exhibited growth defects at concentrations of benomyl permissive for the parent strain, and nine appeared to be tolerant of inhibitory levels of benomyl. All of the mutant strains showed normal sensitivity to ultraviolet and {gamma}-irradiation. Further characterization of these mutant strains will describe the functions of gene products crucial to the successful execution of processes required for aspects of the chromosome cycle that are important for chromosome transmission fidelity in mitosis.

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				S. R. Collins, P. Kemmeren, X.-C. Zhao, J. F. Greenblatt, F. Spencer, F. C. P. Holstege, J. S. Weissman, and N. J. Krogan Toward a Comprehensive Atlas of the Physical Interactome of Saccharomyces cerevisiae Mol. Cell. Proteomics, March 1, 2007; 6(3): 439 - 450. [Abstract] [Full Text] [PDF]

				J. L. Parish, J. Rosa, X. Wang, J. M. Lahti, S. J. Doxsey, and E. J. Androphy The DNA helicase ChlR1 is required for sister chromatid cohesion in mammalian cells J. Cell Sci., December 1, 2006; 119(23): 4857 - 4865. [Abstract] [Full Text] [PDF]

				M. R. Gallas, M. K. Dienhart, R. A. Stuart, and R. M. Long Characterization of Mmp37p, a Saccharomyces cerevisiae Mitochondrial Matrix Protein with a Role in Mitochondrial Protein Import Mol. Biol. Cell, September 1, 2006; 17(9): 4051 - 4062. [Abstract] [Full Text] [PDF]

				B. Montpetit, T. R. Hazbun, S. Fields, and P. Hieter Sumoylation of the budding yeast kinetochore protein Ndc10 is required for Ndc10 spindle localization and regulation of anaphase spindle elongation J. Cell Biol., August 28, 2006; 174(5): 653 - 663. [Abstract] [Full Text] [PDF]

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				B. Montpetit, K. Thorne, I. Barrett, K. Andrews, R. Jadusingh, P. Hieter, and V. Measday Genome-Wide Synthetic Lethal Screens Identify an Interaction Between the Nuclear Envelope Protein, Apq12p, and the Kinetochore in Saccharomyces cerevisiae Genetics, October 1, 2005; 171(2): 489 - 501. [Abstract] [Full Text] [PDF]

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				R. V. Skibbens Unzipped and loaded: the role of DNA helicases and RFC clamp-loading complexes in sister chromatid cohesion J. Cell Biol., June 20, 2005; 169(6): 841 - 846. [Abstract] [Full Text] [PDF]

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				M. Petronczki, B. Chwalla, M. F. Siomos, S. Yokobayashi, W. Helmhart, A. M. Deutschbauer, R. W. Davis, Y. Watanabe, and K. Nasmyth Sister-chromatid cohesion mediated by the alternative RF-CCtf18/Dcc1/Ctf8, the helicase Chl1 and the polymerase-{alpha}-associated protein Ctf4 is essential for chromatid disjunction during meiosis II J. Cell Sci., July 15, 2004; 117(16): 3547 - 3559. [Abstract] [Full Text] [PDF]

				M. C. Rodrigo-Brenni, S. Thomas, D. C. Bouck, and K. B. Kaplan Sgt1p and Skp1p Modulate the Assembly and Turnover of CBF3 Complexes Required for Proper Kinetochore Function Mol. Biol. Cell, July 1, 2004; 15(7): 3366 - 3378. [Abstract] [Full Text] [PDF]

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