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MT Final Castagno Goodman 04.30.18.pdf (3.66 MB)

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A Novel Method to Analyze DNA Breaks and Repair in Human Cells

Goodman, Caitlin Elizabeth
http://rave.ohiolink.edu/etdc/view?acc_num=wright1525086265360859

Abstract Details

2018, Master of Science (MS), Wright State University, Biochemistry and Molecular Biology.
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.
Michael Leffak, Ph.D. (Advisor)
Michael Markey, Ph.D. (Committee Member)
Weiwen Long, Ph.D. (Committee Member)
123 p.
Biochemistry; Molecular Biology
Microsatellite; DNA; Double strand break; DSB; CTG; expanded microsatellite; MUS81; EME1; EME2; CTG CAG; crossover junction endonuclease; trinucleotide repeat; replication stress; hairpin; secondary structure

Recommended Citations

Citations

  • Goodman, C. E. (2018). A Novel Method to Analyze DNA Breaks and Repair in Human Cells [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1525086265360859

    APA Style (7th edition)

  • Goodman, Caitlin. A Novel Method to Analyze DNA Breaks and Repair in Human Cells . 2018. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1525086265360859.

    MLA Style (8th edition)

  • Goodman, Caitlin. "A Novel Method to Analyze DNA Breaks and Repair in Human Cells ." Master's thesis, Wright State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=wright1525086265360859

    Chicago Manual of Style (17th edition)

wright1525086265360859
410
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This open access ETD is published by Wright State University and OhioLINK.