Work

Break-induced replication

Year: 2025
Type: dissertation
Abstract: Break-induced replication (BIR) is a recombination process that repairs DNA breaks that possess only a single end that can find homology in the genome. BIR is an error prone process that is known to promote genome instability and has been implicated in cancer initiation and progression. Here, I use experimental systems in yeast to model two BIR-initiated genome instabilities. First, I investigate the proteins involved in a BIR-driven process that maintains telomeres in the absence of telomerase known as alternative lengthening of telomeres (ALT). Using a telomerase deletion system, I determine that Mph1 and the mismatch repair proteins Msh2 and Mlh1 suppress the formation of ALT survivors or precursors. I show that deletion of the RAD54 gene has a greater effect on ALT frequency than deletion of RAD51. Finally, I develop and optimize a new telomerase shut-off system. This novel system will allow all stages of ALT to be studied.
Language: English
Open Access status: green
OpenAlex ID: W7091611405
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