UBC Theses and Dissertations
DNA:RNA hybrid genome-wide profiling and links to genomic instability Chan, Yujia Alina
DNA:RNA hybrid formation is emerging as a significant cause of genomic instability in biological systems ranging from bacteria to mammals. However, the scope of cellular pathways that prevent DNA:RNA hybrids and the genomic loci prone to hybrid formation are unclear. In Saccharomyces cerevisiae, DNA:RNA hybrids were found to be prevalent in various RNA processing, DNA repair and kinetochore mutants. In particular, mRNA cleavage and polyadenylation factors were demonstrated to maintain genome integrity by preventing transcription-dependent DNA:RNA hybrid formation. Genome-wide profiling of DNA:RNA hybrids showed that highly transcribed genes are prone to hybrid formation in the absence of hybrid-mitigating enzymes. Furthermore, the hybrid profiles highlight various genetic features prone to hybrid formation and suggest potential functions for DNA:RNA hybrids in antisense transcription regulation. Together, these findings elucidate previously unrecognized pathways that mitigate DNA:RNA hybrid formation as well as the characteristics of hybrid prone genomic regions.
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