RNA EXPORT FACTOR ELF1 MAINTAINS GENOME STABILITY IN FISSION YEAST

Genome instability, or frequent mutations within a genome, is deleterious and a hallmark of carcinogenesis. Here, I identified that Elf1, a AAA+ family ATPase involved in mRNA nuclear export, prevents genome instability. Upon deletion, elf1Δ cells grow slowly, forming small colonies. Curiously, they can switch to larger, faster-growing colonies. Genetic analysis revealed that frequent mutations, rather than prions or other epigenetic phenomena, cause the phenotype switching. This suggests Elf1 is required to maintain genome stability. Since RNAs accumulate in the nucleus of elf1Δ cells due to an RNA export defect, I hypothesized that excess RNAs in the nucleus may increase formation of DNA-RNA hybrids, known as R-loops, which have been tied to enhanced mutation rates. Supporting this hypothesis, I found that when elf1Δ cells lost RNase H, preventing R-loop degradation, mutation rates increased over 6-fold. As understanding sources of genome instability is fairly recent, my research may uncover fundamental mechanisms causing genomic instability in cells with impaired mRNA export. Additionally, to further investigate the elf1Δ-alleviating suppressor mutations, I used whole genome sequencing to identify several candidate mutations. Pinpointing the exact mutations which cause the phenotype switching may reveal more about Elf1’s functions.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2017

Author dc:creator

• Drayton, Alena

• chromodomain

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10339/82201

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/82201