Insights into the consequences of chromosome gains and losses in S. cerevisiae

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2016.

Bibliographic Details
Main Author: Beach, Rebecca Ruth
Other Authors: Angelika Amon.
Format: Thesis
Language:eng
Published: Massachusetts Institute of Technology 2016
Subjects:
Online Access:http://hdl.handle.net/1721.1/103162
_version_ 1811068785713479680
author Beach, Rebecca Ruth
author2 Angelika Amon.
author_facet Angelika Amon.
Beach, Rebecca Ruth
author_sort Beach, Rebecca Ruth
collection MIT
description Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2016.
first_indexed 2024-09-23T08:01:05Z
format Thesis
id mit-1721.1/103162
institution Massachusetts Institute of Technology
language eng
last_indexed 2024-09-23T08:01:05Z
publishDate 2016
publisher Massachusetts Institute of Technology
record_format dspace
spelling mit-1721.1/1031622019-04-09T16:08:10Z Insights into the consequences of chromosome gains and losses in S. cerevisiae Beach, Rebecca Ruth Angelika Amon. Massachusetts Institute of Technology. Department of Biology. Massachusetts Institute of Technology. Department of Biology. Biology. Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2016. This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. Cataloged from student-submitted PDF version of thesis. Includes bibliographical references. When cells divide, they must properly duplicate and segregate their genome to generate two identical daughter cells with faithful transmission of the genomic content. Errors in chromosome segregation lead to aneuploidy, a state of chromosomal imbalance where the karyotype is not an exact multiple of the haploid complement. At an organismal level, aneuploidy is the leading cause of miscarriage and developmental defects, while at a cellular level, aneuploidy causes proliferative defects and is detrimental to cell fitness. However, aneuploidy is also associated with cancer, a disease of uncontrolled proliferation. Understanding the effects of aneuploidy on cellular physiology has broad implications for many areas of human health. Here, I have characterized the G1 delay in aneuploid S. cerevisiae. Aneuploid yeast exhibited a growth defect in G1. Additionally, aneuploid cells displayed a cell cycle entry delay due to delayed accumulation of G1 cyclins. Like other cellular stresses, aneuploidy interferes with the cell's ability to grow and to enter the cell cycle. I also developed a novel method to systematically examine the immediate consequences of gaining and-for the first time-losing single or multiple chromosomes. Using this system, I found that phenotypes wide-spread among aneuploid cells develop immediately following chromosome mis-segregation. Also, phenotypes common to chromosome gains are also wide-spread among cells that lost chromosomes, indicating that chromosome gains and losses fundamentally affect cells in similar ways. Finally, cell cycle analyses following chromosome mis-segregation revealed a surprising phenotypic variability among cells harboring the same aneuploidies. Together, these results provide insights into the mechanisms for the observed consequences of chromosome gains and losses on cellular physiology. by Rebecca Ruth Beach. Ph. D. 2016-06-20T17:18:13Z 2016-06-20T17:18:13Z 2016 Thesis http://hdl.handle.net/1721.1/103162 951537357 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 222 pages application/pdf Massachusetts Institute of Technology
spellingShingle Biology.
Beach, Rebecca Ruth
Insights into the consequences of chromosome gains and losses in S. cerevisiae
title Insights into the consequences of chromosome gains and losses in S. cerevisiae
title_full Insights into the consequences of chromosome gains and losses in S. cerevisiae
title_fullStr Insights into the consequences of chromosome gains and losses in S. cerevisiae
title_full_unstemmed Insights into the consequences of chromosome gains and losses in S. cerevisiae
title_short Insights into the consequences of chromosome gains and losses in S. cerevisiae
title_sort insights into the consequences of chromosome gains and losses in s cerevisiae
topic Biology.
url http://hdl.handle.net/1721.1/103162
work_keys_str_mv AT beachrebeccaruth insightsintotheconsequencesofchromosomegainsandlossesinscerevisiae