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Genome Wide DNA Replication Timing in Human Pluripotent and Leukemic Cell Types

Accurate replication of DNA once and only once per cell cycle is an essential process for all living organisms. Despite many studies aimed at understanding this phenomenon, no mechanism describing where and when replication initiates in mammalian cells has yet been elucidated. However, it is well established that DNA is replicated as megabase-sized chromosomal segments called domains in a specific temporal order during S phase. The order in which these segments replicate is called the replication timing program. In recent years, approaches using microarray technology have been developed to study replication timing throughout the entire genome (Hiratani et al., 2008; Hiratani et al., 2010; Woodfine et al., 2004). These approaches have allowed the study of genome-wide replication timing patterns throughout various stages of mouse embryonic stem cell development, and led to the discovery that replication timing is a cell-type specific, developmentally regulated event with epigenetic significance (Hiratani et al., 2010; Ryba et al., 2010). Here I use the genome-wide replication timing assay to study replication timing patterns in human cell types. Specifically, I have investigated whether significant differences in replication timing exist in human embryonic stem cell lines cultured under various growth conditions. In collaboration with other stem cell biologists I have performed genome wide replication timing analysis on primed and naïve human pluripotent cell types. Finally, in a separate but related project, I have used the genome wide replication timing assay to compare replication timing in normal B lymphoblasts to replication timing in established leukemic cell lines and leukemia patient samples in order to probe for the existence of leukemia specific changes in replication timing that may be linked to known genetic subtypes of leukemia or prognoses. / A Thesis Submitted to the Department of Biological Science in Partial Fulfillment
of the Requirements for the Degree of Master of Science. / Spring Semester, 2011. / March 31, 2011. / Leukemia, Pluripotency, Stem Cell, DNA Replication / Includes bibliographical references. / David Gilbert, Professor Directing Thesis; Akash Gunjan, Committee Member; Karen McGinnis, Committee Member; Yanchang Wang, Committee Member.

Identiferoai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_175697
ContributorsBattaglia, Dana (authoraut), Gilbert, David (professor directing thesis), Gunjan, Akash (committee member), McGinnis, Karen (committee member), Wang, Yanchang (committee member), Department of Biological Science (degree granting department), Florida State University (degree granting institution)
PublisherFlorida State University, Florida State University
Source SetsFlorida State University
LanguageEnglish, English
Detected LanguageEnglish
TypeText, text
Format1 online resource, computer, application/pdf
RightsThis Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). The copyright in theses and dissertations completed at Florida State University is held by the students who author them.

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