Schwindt, Eike: The influence of G-quadruplex structures on meiosis. - Bonn, 2021. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5-60767
@phdthesis{handle:20.500.11811/8899,
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5-60767,
author = {{Eike Schwindt}},
title = {The influence of G-quadruplex structures on meiosis},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2021,
month = jan,

note = {Several lines of evidence emphasize the potential function of G-quadruplex (G4) structures during DNA replication, transcription and recombination. Although there are experimental evidences that G4s play a role during meiosis, the question if G4 structures influence meiosis has not been ad-dressed yet. Meiosis is a specialized cell division of eukaryotic germ cells. It consists of a single DNA replication followed by two cell divisions, which results in four gametes with a haploid chromosome set. By this, parental cells can pass on its genetic material from generation to generation without leading to aneuploidy.
In this thesis I aimed to identify and characterize the impact of G4 structure formation during meiosis in Saccharomyces cerevisiae. I mapped genome-wide the occurrence of G4 structure during vegetative growth and meiosis by G4-chromatin immunoprecipitation (ChIP)-seq and I identified 115 robust G4 binding proteins, which act during meiosis. Additionally, I analyzed the proteome of cells during meiosis and cells that were treated with the G4-stabilizing chemical compound Phen-DC3. Several proteins were specific for each data set down- or upregulated, respectively. This argues for an altered protein expression upon G4 stabilization.
Further, stabilization of G4 structures by adding Phen-DC3 to meiotic yeast cells in vivo led to cell cycle arrest between G1 and pre-meiotic S-phase. In subsequent experiments I shed light on the cause of this arrest upon G4 stabilization. In the past it was shown that G4s often act as obstacles and consequently, resulting in genome instability. Therefore, I tested if G4 stabilization leads to genome instability during meiosis and consequently to an activation of the G1/S-checkpoint and G1 arrest. Interestingly, deletion of the checkpoint proteins Mec1 and Tel1 did not rescue the observed phenotype, demonstrating a G4 stabilization caused G1 arrest, which is independent of checkpoint activation.
It was demonstrated that preferred meiotic double-strand break (DSB) sites, termed as hot spots overlap with regions, which are prone to fold into G4 structures. Meiotic DSBs are essential for the proper segregation of the homologue chromosomes during meiosis I. The overlap between meiotic DSB hot spots and G4 motifs led to the hypothesis that G4s are involved in meiotic DSB formation. For this reason, I evaluated the meiotic DSB frequency at meiotic DSB hot spot HIS4 in dependency of G4 motifs. During this thesis I discovered that meiotic DSBs are induced independently of G4 motifs at HIS4, which indicates that G4s do not play a direct role in DSB formation during meiosis.},

url = {https://hdl.handle.net/20.500.11811/8899}
}

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