thesis

Roles for Condensin in C. elegans Chromosome Dynamics.

Abstract

Condensin complexes are essential for higher order organization of chromosome structure. Higher eukaryotes have two condensins (condensin I and II) dedicated to mitotic and meiotic chromosome dynamics. C. elegans was thought to be an anomaly, with only a single mitotic condensin (condensin II), and one specialized for dosage compensation (condensin IDC). Condensin IDC binds both hermaphrodite X chromosomes to reduce gene expression by half, equalizing X-linked gene product in males (XO) and hermaphrodites (XX), while condensin II is essential for efficient chromosome organization and segregation during mitosis and meiosis. It was proposed that the unusual holocentric chromosomes in C. elegans did not require condensin I and II to accomplish cell division, and therefore, condensin I was customized for X chromosome regulation. However, we showed that subunits from condensin IDC and condensin II interact to form a second mitotic/meiotic condensin, the bonafide C. elegans condensin I. Our findings raise C. elegans to a unique status, with three distinct condensins controlling holocentric chromosome dynamics. Condensin I and II have distinct localization patterns on mitotic and meiotic chromosomes, suggesting that their roles in chromosome organization may be distinct. During mitosis, condensin II colocalizes with the centromere while condensin I discontinuously coats chromosomes. Condensin I, but not II, colocalizes with aurora B kinase, AIR-2, and our data suggests that in mitosis, AIR-2 activity is required for the recruitment of condensin I, but not condensin II. In meiosis, condensin II localizes to the sister chromatid core, while condensin I localizes to the interface between homologous chromosomes. Condensin I and AIR-2 colocalize at this interface. Similar to mitosis, in AIR-2 depleted animals undergoing meiosis, condensin II is not affected but condensin I mislocalizes to the interface between sister chromatids, as well as homologous chromosomes. This work indicates that AIR-2 provides important spatial cues for condensin I localization on meiotic chromosomes. The contribution of condensin I to during mitosis and meiosis is not well-defined. A comparative analysis of chromosome organization and mitotic/ meiotic progression between wildtype and condensin I depleted animals will provide a better understanding of condensin I function in chromosome dynamics during cell division.Ph.D.Molecular, Cellular, and Developmental BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/89697/1/karishms_1.pd

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