The Role of Histone H4 Acetylation in DNA Replication in Schizosaccharomyces Pombe
Open Access
Author:
Harper, Logan James
Area of Honors:
Microbiology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
Song Tan, Thesis Supervisor Eishi Noguchi, Thesis Supervisor Song Tan, Thesis Supervisor Dr. Sarah Ellen Ades, Thesis Honors Advisor Scott Brian Selleck, Faculty Reader
Keywords:
Histone Acetylation DNA Replication
Abstract:
The dynamic addition and removal of acetyl groups to lysine residues on histone proteins is one of the critical events that modulate DNA structure. This process, called “histone acetylation”, has been known to impact the regulation of transcription, but its role in DNA replication is not well understood. Here I report on my study of histone H4 acetylation in the fission yeast Schizosaccharomyces pombe. Using the two-hybrid method for detecting protein-protein interactions, it was demonstrated that Swi1, a component of the replication fork protection complex, interacts with a NuA4 histone acetyltransferase complex subunit, Vid21. Using quantitative Western blot I show that the level of bulk histone H4 acetylation is greatly reduced in the absence of Swi1 or Vid21. Furthermore, the cell-cycle dependent histone H4 acetylation was deregulated in swi1 and vid21 mutants. Importantly, mutations at acetylation sites in histone H4 rendered cells highly sensitive to camptothecin, a compound that induces replication fork breakage. These results suggest that histone H4 acetylation has critical roles in regulation of DNA replication and replication fork repair used to preserve genomic integrity.
