Austin Macklem MSc Student, Aristizabal Lab Uncovering the functional consequences of cancer associated histone H2B mutations In eukaryotes DNA is wrapped into chromatin, a nucleoprotein structure that controls DNA-templated processes like DNA replication, transcription and DNA repair. Nucleosomes are the basic unit of chromatin and consist of 146 base pairs of DNA wrapped around two copies of histone H2A, H2B, H3, H4. The increased availability of cancer genomics datasets has revealed a large repertoire of mutations on histone genes and shown that these occur frequently in cancer patients. Although, the significance of the large histone gene mutational landscape remains understudied, some of these mutations (H3K27M, H3K36M and H3G34R) have been shown to drive oncogenesis and are now used as biomarkers of specific tumor types. My project aims to advance our understanding of the functional consequences of cancer-associated histone mutations using Saccharomyces cerevisiae as a model system. To this end, we have mined The Cancer Genome Atlas (TCGA) and identified cancer-associated mutations on histone H2B, a histone that remains poorly characterized with regards to cancer-associated histone mutations. Focusing on mutations that fall on residues conserved between yeast and humans, I have generated a panel of strains carrying only mutant or mutant and wild type version of H2B. These strains will be examined for effects on growth, chromatin structure and function in vivo.
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