University of Texas Health Science Center at Houston
Histone H3 K4 Methylation Regulates The Spindle Assembly Checkpoint Through Direct Binding of Multiple Checkpoint Components and Cdc20
Abstract
dc:description.abstract<p>Histone H3K4 methylation is conserved across species and is associated with active transcription. By using <em>Saccharomyces cerevisiae</em>, we found histone H3K4 methylation has a previously unknown role in regulating mitosis through the Spindle Assembly Checkpoint. The Spindle Assembly Checkpoint ensures duplicated chromosomes are segregated correctly and each daughter cell receives one full copy of the genome. Our data show <em>SET1 </em>mutants and histone H3K4 mutants display a resistance to the mitotic poison, benomyl. Moreover methylated histone H3 directly binds to Spindle Assembly Checkpoint proteins Bub3 and Mad2 as well as the activator of the Anaphase Promoting Complex (APC) protein Cdc20. <em>MAD2</em> encodes a HORMA domain, which I identify as a novel histone binding motif. Mad2 maintains two differing conformations, closed Mad2 (C-Mad2) and open Mad2 (O-Mad2). We find C-Mad2 increases the Mad2-H3 interaction. In addition, O-Mad2 limits the H3-Mad2 interaction. Further analysis, shows C-Mad2 can bind to all unmodified, mono-, di-, and tri-methylated H3K4 while O-Mad2 loses H3 binding ability when H3K4 is di- or tri-methylated. Here we show H3K4 methylation inhibits the Spindle Assembly Checkpoint from correctly deactivating after cell cycle arrest by binding C-Mad2.</p>
Degree
thesis:*- Name thesis:degree_name
- Doctor of Philosophy (PhD)
- Level thesis:degree_level
- Dissertation (PhD)
- Year dc:date.available
- 2015
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Schibler, Andria C
- Contributors dc:contributor
-
- Sharon Y.R. Dent, Ph.D.
- Mark T. Bedford, Ph.D.
- Jill Schumacher, Ph.D.
Subjects
dc:subject × 10Identifiers
dc:identifier.*- Repository record dc:identifier
- https://digitalcommons.library.tmc.edu/utgsbs_dissertations/628
- OAI identifier oai:identifier
- oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1663