First Advisor

Justin Courcelle

Term of Graduation

Summer 2026

Date of Publication

9-21-2026

Document Type

Thesis

Degree Name

Master of Science (M.S.) in Biology

Department

Biology

Language

English

Subjects

Cancer, Escherichia coli, Genetics, Saccharomyces cerevisiae

Physical Description

1 online resource (vi, 143 pages)

Abstract

Accurate completion of DNA replication when forks converge is essential for genome stability. In Escherichia coli, several proteins have been identified including RecG, ExoI, RecBCD, and SbcCD, that contribute to completing replication, and loss of these factors causes genetic instability. Eukaryotes encode proteins with homology to several E. coli completion enzymes. Mre11–Rad50 complex is structurally and functionally conserved with bacterial SbcCD, and Rrm3 shares homologous motifs with bacterial RecBCD. These proteins are often described as being involved in homologous double strand break repair. Whether they are also conserved and play a similar role as their E. coli counterparts in completing DNA replication has not been examined. Using Saccharomyces cerevisiae, this study examined whether Mre11–Rad50 and Rrm3 play roles in replication completion and genome maintenance. Mutants lacking Mre11 displayed reduced viability, accumulation of enlarged late G2 populations, and instability of telomeric, plasmid, and mitochondrial DNA. Rrm3 mutants displayed difficulty progressing through S phase and also had abnormalities associated with plasmid and mitochondrial replication. These phenotypes would be consistent with mutations that impair replication completion. However, when I examined the replication profiles of the mutants, neither Δmre11 or Δrrm3 strains exhibited pronounced abnormalities at chromosomal replication termination regions as might be expected, and overall replication timing profiles remained broadly similar to wild type.

Aspects of These findings are suggestive of a role for Mre11 and Rrm3 in contributing to completing DNA replication, however it remains inconclusive at this point as the mutants do not exhibit clear chromosomal abnormalities at these completion loci analogous to the mutants in bacterial systems. I discuss the possibility of how mutations in other gene products may be required to observe the copy number abnormalities at these loci. I also discuss the alternative possibility that the large number of completion loci in eukaryotic organisms, would result in a lethal phenotype in eukaryotic cells, or that other gene products may partially compensate and minimize these defects at in the mutants I examined.

Rights

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Persistent Identifier

https://archives.pdx.edu/ds/psu/45166

Included in

Biology Commons

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