Date of Award

12-2007

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Biochemistry and Cellular and Molecular Biology

Major Professor

Bruce D. McKee

Committee Members

Ranjan Ganguly, Jae Park, Mariano Labrador, Yisong Wang

Abstract

Sister chromatid cohesion is essential for proper chromosome segregation during meiosis. However, the mechanism of meiotic cohesion in Drosophila is unclear.

We describe a novel protein, SOLO (Sisters On the LOose) that is essential for meiotic cohesion in Drosophila melanogaster. solo mutations cause high nondisjunction of sister and homologous chromatids of sex chromosomes and autosomes in both sexes. In solo males, sister chromatids separate prematurely and segregate randomly during meiosis II. Although bivalents appear intact throughout meiosis I, sister centromeres lose cohesion prior to prometaphase I and orient nearly randomly on the meiosis I spindle. Centromeric foci of SMC1 are absent in solo males at all meiotic stages. SOLO and the cohesin protein SMC1 co-localize to meiotic centromeres from early prophase I until anaphase II in wild-type males but both proteins are removed prematurely from centromeres at anaphase I in mei-S332 mutants, coincident with premature loss of cohesion in those mutants.

solo mutations in females cause reduced frequency of homologous recombination between X chromosomes and autosomes, partially due to the loss of inhibition of sister chromatid exchange. Synaptonemal complex assembly is severely disrupted in early meiotic stage in solo females. SOLO colocalizes with SMC1 and C(3)G in meiosis. Additionally, SOLO is required for stabilizing chiasmata generated from residual recombination events.

The data about the phenotypes of solo males and females and colocalization patterns of SOLO strongly suggest SOLO is a component of potential cohesin in Drosophila meiosis.

Drosophila males undergo meiosis without recombination. However, the underlying mechanism is not known. Mutations of vasa cause high frequency of X-Y exchange in meiosis. Chromatin bridges at anaphase I and II, due to dicentric recombination events, were observed in vasa males. vas and solo double mutant showed precocious segregation of homologs at metaphase I besides chromatin bridge at anaphase I and II. Our data thus for the first time demonstrate that inhibition of meiotic recombination during male meiosis requires vas function and interactions between vas and solo regulate chromosome dynamics in male meiosis.

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