Human cohesin dynamics and their regulation in M and S phase
type: CreativeWork
description: Cohesin is a multimeric ring complex, which associates with DNA throughout most of the eukaryotic cell cycle. Its canonical role is to hold the two copies (sister chromatids) of each chromosome together from the time of their generation in S phase until their separation in M phase, thus ensuring the fidelity of mitosis. The complex mediates this so-called cohesion by topologically embracing the sister chromatids inside its ring structure composed of the three subunits Scc1, Smc1 and Smc3. For this thesis, I have studied cohesin's dynamic association with chromatin in M and S phase as well as its role at the mitotic centrosome, the main microtubule-organizing center of most eukaryotic cells. In order to separate sister chromatids in mitosis, cohesin must be removed from chromosomes. This is ultimately achieved by the action of the cystein protease separase, which cleaves cohesin at the centromeres (the primary constriction site of mitotic chromosomes) to release DNA. In vertebrates, however, the bulk of cohesin molecules, which is located on chromosome arms, is already removed from DNA in the first stage of mitosis, prophase, by a non-proteolytic mechanism called the prophase pathway. Since cohesin embraces the sister chromatids, prophase pathway signaling requires the ring to open up at at least one of its three subunit interaction sites ("gates"). However, which gate opens up for DNA exit has remained enigmatic. The same is true (at least in humans) for cohesin's DNA entry gate, which would be required to open up to topologically reload the ring complex after chromatid separation in telophase. For my thesis, I set out to identify cohesin's DNA exit (prophase) and entry (telophase) gates by employing the so-called FRB/FKBP system, allowing me to artificially close each of cohesin's gates individually in a conditional manner. I found that cohesin's DNA exit gate during prophase is composed of Smc3 and Scc1. To load the complex onto DNA, however, the gate situated bet…
abstract: Cohesin is a multimeric ring complex, which associates with DNA throughout most of the eukaryotic cell cycle. Its canonical role is to hold the two copies (sister chromatids) of each chromosome together from the time of their generation in S phase until their separation in M phase, thus ensuring the fidelity of mitosis. The complex mediates this so-called cohesion by topologically embracing the sister chromatids inside its ring structure composed of the three subunits Scc1, Smc1 and Smc3. For this thesis, I have studied cohesin's dynamic association with chromatin in M and S phase as well as its role at the mitotic centrosome, the main microtubule-organizing center of most eukaryotic cells. In order to separate sister chromatids in mitosis, cohesin must be removed from chromosomes. This is ultimately achieved by the action of the cystein protease separase, which cleaves cohesin at the centromeres (the primary constriction site of mitotic chromosomes) to release DNA. In vertebrates, however, the bulk of cohesin molecules, which is located on chromosome arms, is already removed from DNA in the first stage of mitosis, prophase, by a non-proteolytic mechanism called the prophase pathway. Since cohesin embraces the sister chromatids, prophase pathway signaling requires the ring to open up at at least one of its three subunit interaction sites ("gates"). However, which gate opens up for DNA exit has remained enigmatic. The same is true (at least in humans) for cohesin's DNA entry gate, which would be required to open up to topologically reload the ring complex after chromatid separation in telophase. For my thesis, I set out to identify cohesin's DNA exit (prophase) and entry (telophase) gates by employing the so-called FRB/FKBP system, allowing me to artificially close each of cohesin's gates individually in a conditional manner. I found that cohesin's DNA exit gate during prophase is composed of Smc3 and Scc1. To load the complex onto DNA, however, the gate situated bet…
author: Buheitel, Johannes
date published: 2015-10-14
date modified: 2026-07-27T18:49:49Z
provider: Universität Bayreuth
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Universität Bayreuth