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Eukaryotic Cell, October 2002, p. 758-773, Vol. 1, No. 5
1535-9778/02/$04.00+0     DOI: 10.1128/EC.1.5.758-773.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

mcl1+, the Schizosaccharomyces pombe Homologue of CTF4, Is Important for Chromosome Replication, Cohesion, and Segregation

Dewight R. Williams* and J. Richard McIntosh

Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309-0347

Received 5 April 2002/ Accepted 26 June 2002

The fission yeast minichromosome loss mutant mcl1-1 was identified in a screen for mutants defective in chromosome segregation. Missegregation of the chromosomes in mcl1-1 mutant cells results from decreased centromeric cohesion between sister chromatids. mcl1+ encodes a ß-transducin-like protein with similarity to a family of eukaryotic proteins that includes Ctf4p from Saccharomyces cerevisiae, sepB from Aspergillus nidulans, and AND-1 from humans. The previously identified fungal members of this protein family also have chromosome segregation defects, but they primarily affect DNA metabolism. Chromosomes from mcl1-1 cells were heterogeneous in size or structure on pulsed-field electrophoresis gels and had elongated heterogeneous telomeres. mcl1-1 was lethal in combination with the DNA checkpoint mutations rad3{Delta} and rad26{Delta}, demonstrating that loss of Mcl1p function leads to DNA damage. mcl1-1 showed an acute sensitivity to DNA damage that affects S-phase progression. It interacts genetically with replication components and causes an S-phase delay when overexpressed. We propose that Mcl1p, like Ctf4p, has a role in regulating DNA replication complexes.

* Corresponding author. Mailing address: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347. Phone: (303) 492-8536. Fax: (303) 492-7744. E-mail: De.Williams{at}Colorado.edu.

Eukaryotic Cell, October 2002, p. 758-773, Vol. 1, No. 5
1535-9778/02/$04.00+0     DOI: 10.1128/EC.1.5.758-773.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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