Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/138381
Title: THE IMPORTANCE OF INHIBITORY PHOSPHORYLATION OF CDK1 ON GENOMIC INTEGRITY
Authors: RADOSLAW SEBASTIAN SZMYD
Keywords: Cdk1, Cdk1AF, DNA damage, Mus81, genomic instability
Issue Date: 4-Aug-2017
Citation: RADOSLAW SEBASTIAN SZMYD (2017-08-04). THE IMPORTANCE OF INHIBITORY PHOSPHORYLATION OF CDK1 ON GENOMIC INTEGRITY. ScholarBank@NUS Repository.
Abstract: Faithful replication of genetic material and chromosome segregation prior cell division are timely regulated within eukaryotic cell cycle. Proteins that orchestrate cell cycle progression are cyclin-dependent kinases (Cdks), which activity is regulated by association with cyclins. In my thesis, I investigated the importance of inhibitory phosphorylation of Cdk1 on cell cycle progression and genomic integrity using the conditional Cdk1T14AY15F knockin mouse model. In this model, two inhibitory phosphorylation sites were replaced by non-phosphorylatable amino acids generating resistant to inhibitory phosphorylation version of Cdk1, referred to as Cdk1AF. It has been demonstrated that in vivo expression of Cdk1AF is embryonic lethal. To unravel the underlying mechanism, I isolated primary mouse embryonic fibroblasts (MEFs). An induced expression of Cdk1AF in MEFs is associated with elevated level of DNA damage and leads to Mus81-mediated chromosomal fragmentation in S phase. My results highlight the importance of temporal regulation of Cdk1 activity on genomic stability.
URI: http://scholarbank.nus.edu.sg/handle/10635/138381
Appears in Collections:Ph.D Theses (Open)

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