Histone H2A.Z, a variant of histone H2A, is important for the functional integrity of the cell: deletion of HTZ1 in S. cerevisiae results in plasmid and chromosome loss, increased susceptibility to DNA damage, flaws in sister chromatid cohesion in mitosis, and various other defects. Deletion of HHO1, which encodes the linker-histone H1, in htz1Δ, has been observed to suppress some of these defects. Can deletion of HHO1 rescue defects in DNA damage repair and cell-cycle progression in htz1Δ strains? Additionally, are there other possible genes mediating the HHO1-HTZ1 relationship? To answer these questions, we performed serial dilution growth assays with various DNA-damaging and cell-cycle inhibiting drugs, as well as a plasmid-based non-homologous end-joining assay on strains with HHO1 and/or HTZ1 deleted. Results indicate that deleting HHO1 in htz1Δ can partially suppress defects in DSB repair and in cell-cycle progression. However, we have yet to identify a possible genetic mediator between HTZ1 and HHO1. A possible model is that in the absence of H2A.Z, H1 limits access to the DNA, thus hindering the progress of the DNA repair machinery and factors that encourage cell-cycle progression. Can the pattern of suppression between HHO1 and HTZ1 therefore be explained by changes in global chromatin compaction and nucleosome turnover rate? To address these questions, we developed a chromatin comet-assay to measure global chromatin compaction, and a ChIP assay against H3 to quantify nucleosome turnover. We have not finished assay development, and future work should focus on addressing technical issues.
"},{"label":"Degree","value":["Bachelor of Arts with Departmental Honors"]},{"label":"Administrative Note","value":"Drupal Node ID: 23899