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Title: Evolutionary and Functional Analysis of TMAC: A Drosophila Transcriptional Regulatory Complex
Author: Doggett, Karen
ISNI:       0000 0001 3427 2336
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2008
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The testis meiotic arrest genes regulate transcription of genes required for entry into meiosis and spermatid differentiation. This is achieved by the formation of the multisubunit testis meiotic arrest complex, TMAC. Two components of this complex Mip40 and Caf1 are also found in the Drosophila Rb, E2F and Myb (dREAM) complex which acts to regulate transcription of differentiation genes in the soma and female germline. I have shown that two TMAC proteins have paralogues in the dREAM complex; aly/mip130 and tomb/mip120. A further dREAM complex component, Iin52 is a paralogue of the testis specific gene wuc/CG12442. I have investigated the timings of these three duplications in diptera evolution and propose a model for the stepwise evolution of the complexes, followed by the repeated subfunctionalisation from the ancestral ubiquitous expression to one testis specific complex and one complex functioning in the soma and female germline. In addition to wuc being paralogous to Iin52 it has also been found to bind the TMAC protein Aly by yeast-two-hybrid. Wuc protein localises to chromatin in primary spermatocytes but in a tomb (TMAC, DNA-binding protein) mutant background this specific localisation. is lost. I have investigated wuc's RNAi phenotype in the testis and flies are male sterile. Some meiosis occurred, but multiple chromosome segregation defects and no signs of differentiation/elongation were observed. Primary spermatocytes also accumulated an unidentified phase dark granular material in the cytoplasm and homologous chromosome pairing was disrupted. The expression of multiple TMAC target genes are also decreased in wuc RNAi testes which with all the above evidence suggests wuc is a potential new meiotic arrest gene.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available