Publication Date
2018
Document Type
Thesis
Committee Members
Michael Leffak (Advisor), Weiwen Long (Committee Member), Michael Markey (Committee Member)
Degree Name
Master of Science (MS)
Abstract
Microsatellites repeat sequences are prone to forming non-canonical DNA structures and mutations. These areas of the genome can undergo expansions and contractions and are responsible for a variety of inherited neurological and neuromuscular disorders. Hairpin structures formed by trinucleotide repeats can lead to replication fork stalling, and fork collapse causing DNA double strand breaks. Various mechanisms are involved in processing microsatellites including mismatch repair, base excision repair, and crossover junction endonuclease cleavage. These processes, which are supposed to protect the genome, could also be the culprits which are causing mutations. In order to test and study this hypothesis, the use of a two color marker gene assay to detect DNA double strand breaks at trinucleotide repeats, was used to detect replication fork stalling, and collapse in presence or absence of replication stress. An important mechanism for the restart of a stalled replication fork involves crossover junction endonucleases, which cleave obstacles that prevent passage of the replication fork. This process is led by MUS81 and its associates EME1 and EME2, which form complexes to process these secondary structures allowing the replication fork to progress. My results indicate distinct roles for MUS81-EME1 and MUS81-EME2 complexes in the maintenance of genome stability.
Page Count
123
Department or Program
Department of Biochemistry and Molecular Biology
Year Degree Awarded
2018
Copyright
Copyright 2018, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.
