Cary, Joshua R.
Josh is in the Department of Molecular, Cell and Developmental Biology. He joined the Training Program in 2011. His research mentor is Dr. Steven Jacobsen. He received a B.S. degree in 2007 from UCLA.
Mentor: Dr. Steven Jacobsen
The role of epigenetic modifications in the regulation of gene transcription has been widely studied, yet much less is currently known about the mechanisms by which chromatin states may regulate other DNA processes such as DNA replication. Recent work in Arabidopsis thaliana has uncovered two SET domain proteins, ATXR5 and ATXR6, which have redundant function in catalyzing the monomethylation of histone 3 lysine 27 (H327me1). In double mutant atxr56 plants, the levels of this histone mark are reduced and certain regions of the genome re-replicate, or produce extra DNA copies due to aberrant initiation of replication at origins. Thus, the H3K27me1 modification appears to be necessary for proper duplication of the genome during the cell cycle. In order to further understand the pathway by which ATXR proteins regulate DNA replication, I will use immunoprecipitation followed by mass spectrometry. This approach will attempt to identify other important ATXR pathway proteins: those that form a complex with ATXR in order to write the H3K27me1 mark, and those which bind the mark in order to produce downstream outputs. Genetic screens for suppression of the atxr56 re-replication phenotype may provide additional pathway components. This work should generate deeper insights into the mechanisms cells use to ensure successful replication of the genome during the cell cycle.
