Dissertation/Thesis Abstract

The Polycomb Group Complex PRC1 collaborates with cohesin to stabilize the synaptonemal complex and promote crossovers during meiosis
by Zhou, Pei, Ph.D., Dartmouth College, 2012, 166; 3518592
Abstract (Summary)

dRING is an essential protein encoded by the Polycomb Group (PcG) gene, Sex combs extra (Sce), and functions as a core subunit of the Drosophila Polycomb Repressive Complex 1 (PRC1). PcGs are required for developmentally regulated silencing of target genes. Previous work in our laboratory identified dRING as an interactor of ORD, a Drosophila protein required for meiotic sister-chromatid. To investigate the role of dRING/PRC1 during meiosis, I utilized a FLP/FRT strategy to generate germ-line clones for two Sce mutations, a truncation allele that deletes the ORD interaction domain (Sce 1) and a point mutation that ablates the E3 ligase activity of dRING (the Sce33M2). Oocytes homozygous for either Sce allele exhibit premature disassembly of the synaptonemal complex (SC), a proteinaceous structure that assembles along the length of meiotic chromosomes during prophase I and is required for normal levels of recombination. Meiotic cohesion proteins play an essential role in SC formation and maintenance, and like Sce mutations, disruption of ORD activity leads to SC defects. I also observed premature disassembly of the SC when I simultaneously lowered the dosage of dRING and the cohesin complex subunit, SMC1. Moreover, I detect similar defects when other PRC1 subunits (Psc, Pc) are mutated in combination with cohesin reduction. I uncovered a mild non-uniform reduction in crossover frequency in Sce1 heterozygous oocytes even in the absence of SC defects. However, alteration of the crossover distribution in Sce 1 heterozygotes does not appear to be caused by in increase in sister chromatid exchange. Furthermore, SMC1 immunostaining indicates that when the SC disassembles prematurely in Sce1 germ-line clones and Sce1/smc1Δ oocytes, cohesin-enriched chromosome cores remain intact. My data argue that dRING/PRC1 collaborates with the cohesin complex to maintain the synaptonemal complex and promote normal levels of meiotic recombination by stabilizing the association of homologous chromosomes within the context of the SC. I present a working model in which PRC1 interacts with cohesion proteins that are enriched along the lateral elements of the SC and functions to promote the stable association of homologs in a manner analogous to its role in pairing sensitive silencing in somatic cells.

Indexing (document details)
Advisor: Bickel, Sharon E.
Commitee: Bosco, Giovanni, Compton, Duane, Gladfelter, Amy
School: Dartmouth College
Department: Biology
School Location: United States -- New Hampshire
Source: DAI-B 73/12(E), Dissertation Abstracts International
Subjects: Genetics, Cellular biology
Keywords: Cohesin, Meiosis, Polycomb group complexes, Synaptonemal complex
Publication Number: 3518592
ISBN: 9781267502629
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