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Rejuvenation of cohesion during meiotic prophase is required for maintenance of chiasmata and accurate chromosome segregation / by Katherine Adalia Weng.

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Author	Weng, Katherine Adalia.
Title	Rejuvenation of cohesion during meiotic prophase is required for maintenance of chiasmata and accurate chromosome segregation / by Katherine Adalia Weng.
Date	2013
Abstract	Accurate chromosome segregation in human oocytes requires that meiotic sister chromatid cohesion remain intact for decades and work in model organisms indicates that deterioration of meiotic cohesion over time may be a major determinant of age-related segregation errors. I used Drosophila oocytes to investigate whether oocytes rely exclusively on cohesive linkages that are established during meiotic S phase or if maintenance of meiotic cohesion is an active process that requires rejuvenation throughout the extended period of prophase. I. Deco is the Drosophila homolog of the yeast cohesion establishment factor, Ecol 1, which is required to establish cohesive linkages during S phase. To test the hypothesis that Deco is required for maintenance of meiotic cohesion, I used a Gal4/UAS inducible approach to knock down Deco after meiotic S phase in the female germline. I found that reduction of Deco after meiotic S phase causes premature disassembly of the synaptonemal complex (SC) and increased levels of meiotic nondisjunction (NDJ). Additionally, although chiasmata are formed, they are not maintained. Moreover, SC defects and increased NDJ also occur when cohesin subunits (SMCl, SMC3, SA) and the cohesion loader, Nipped-B are knocked down after meiotic cohesion is established. These data argue that rejuvenation of cohesion requires the loading of new cohesin complexes during meiotic prophase to stabilize chiasmata and ensure proper segregation of meiotic chromosomes. My data also indicate that Deco-mediated cohesion rejuvenation during prophase I is necessary even in the absence of mieotic double-strand breaks (mei-W68 mutant) and therefore differs from the damage-induced cohesion re-establishment pathway that operates during G2 in yeast vegetative cells. Experiments to investigate the mechanism of cohesion rejuvenation suggest that the conserved lysines of SMC3 and the acetyltransferase activity of Deco may play a role during cohesion rejuvenation. Although additional experiments to examine the mechanism of rejuve
Description	xviii, 249 leaves : ill. (some col.) 28 cm.
Format	application/pdf
Advisor	Sharon Bickel, Amy Gladfelter, Yashi Ahmed, Amy MacQueen
College	Dartmouth College. Department of Biological Sciences.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.1012

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Rejuvenation of cohesion during meiotic prophase is required for maintenance of chiasmata and accurate chromosome segregation / by Katherine Adalia Weng.

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