Publication Date

2016

Document Type

Thesis

Committee Members

Michael Leffak (Advisor), Michael Markey (Committee Member), John Paietta (Committee Member)

Degree Name

Master of Science (MS)

Abstract

Trinucleotide repeats (TNRs) are sequences prone to formation of non-B DNA structures and mutations; undergo expansions in vivo to cause various inherited neurodegenerative diseases. Hairpin structures formed during DNA replication or repair can cause replication fork stalling and if left unrepaired could cause single or double strand DNA breaks. To test and study this hypothesis we have devised a novel two color marker gene assay to detect DNA breaks at TNRs. By inducing replication stress our results show that TNRs are prone to DNA strand breaks and it is dependent on the repeat tract length. Double strand breaks at structured DNA are repaired differently than `clean' DSBs. The cells which undergo breaks die off, possibly due to inability to repair breaks. Translesion polymerases help tolerate DNA damage at TNR region.

Page Count

108

Department or Program

Department of Biochemistry and Molecular Biology

Year Degree Awarded

2016


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