The eukaryotic SMC (structural maintenance of chromosomes) proteins and associated subunits form two types of complexes in eukaryotic organisms, including budding yeast. These protein complexes, termed cohesin and condensin, largely determine chromosome structure in mitotically dividing cells. Condensin localisation and high-resolution ChIP analysis revealed that the rDNA locus is the primary target of condensin activity in vivo. We undertook genetic and cytological screens for the factors required for mitosis-specific binding of condensin to chromatin. We identified a range of cis?factors responsible for mitosis-specific condensin targeting to rDNA chromatin. Among them were cell-cycle regulators and chromatin proteins. Alanine-scanning mutagenesis of Mcd1p, a subunit of mitotic cohesin, identified domains responsible for establishment and dissolution of sister chromatid cohesion. The S. cerevisiae mitotic cohesin complex was reconstituted from recombinant subunits. We also reconstituted the hypothetical meiotic cohesin. Analysis of somatic pairing between yeast chromosomes in live cells led to the discovery of interchromosome transassociations, a DNA-homology-dependent mechanism, mediating transient but reproducible interaction between ectopic chromosomal sites in the genome.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2000
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Indirect Cost
Name
U.S. National Inst/Child Hlth/Human Dev
Department
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United States
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Samoshkin, Alexander; Dulev, Stanimir; Loukinov, Dmitry et al. (2012) Condensin dysfunction in human cells induces nonrandom chromosomal breaks in anaphase, with distinct patterns for both unique and repeated genomic regions. Chromosoma 121:191-9
Takahashi, Yoshimitsu; Iwase, Masayuki; Strunnikov, Alexander V et al. (2008) Cytoplasmic sumoylation by PIAS-type Siz1-SUMO ligase. Cell Cycle 7:1738-44
Dulev, Stanimir; Aragon, Luis; Strunnikov, Alexander (2008) Unreplicated DNA in mitosis precludes condensin binding and chromosome condensation in S. cerevisiae. Front Biosci 13:5838-46
Takahashi, Yoshimitsu; Strunnikov, Alexander (2008) In vivo modeling of polysumoylation uncovers targeting of Topoisomerase II to the nucleolus via optimal level of SUMO modification. Chromosoma 117:189-98
Wang, Bi-Dar; Strunnikov, Alexander (2008) Transcriptional homogenization of rDNA repeats in the episome-based nucleolus induces genome-wide changes in the chromosomal distribution of condensin. Plasmid 59:45-53
Yong-Gonzalez, Vladimir; Wang, Bi-Dar; Butylin, Pavel et al. (2007) Condensin function at centromere chromatin facilitates proper kinetochore tension and ensures correct mitotic segregation of sister chromatids. Genes Cells 12:1075-90
Strunnikov, Alexander V (2006) SMC complexes in bacterial chromosome condensation and segregation. Plasmid 55:135-44
Takahashi, Yoshimitsu; Yong-Gonzalez, Vladimir; Kikuchi, Yoshiko et al. (2006) SIZ1/SIZ2 control of chromosome transmission fidelity is mediated by the sumoylation of topoisomerase II. Genetics 172:783-94
Quimby, B B; Yong-Gonzalez, V; Anan, T et al. (2006) The promyelocytic leukemia protein stimulates SUMO conjugation in yeast. Oncogene 25:2999-3005
Wang, Bi-Dar; Butylin, Pavel; Strunnikov, Alexander (2006) Condensin function in mitotic nucleolar segregation is regulated by rDNA transcription. Cell Cycle 5:2260-7

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