Doctor of Philosophy (PhD)
The DNA of eukaryotic cells does not exist in free linear strands; it is tightly packaged and wrapped around nuclear proteins in order to be accommodated it inside the nucleus. The basal repeating unit of chromatin, termed the nucleosome, provides the first level of compaction of DNA into the nucleus. Nucleosomes are interconnected by linker DNA and associated linker histones to form 30 nm fibers. The highly diverse linker histones are critical for compaction and stabilization of higher order chromatin structure by binding DNA entering and exiting the nucleosome. The lysine-rich C-terminal domain (CTD) of metazoan H1 is crucial for such stabilization. This study concerns the functions of Saccharomyces cerevisiae Hmo1p, an high mobility group (HMGB) family protein unique in containing a terminal lysine-rich domain and functions in stabilizing genomic DNA. My study suggests that Hmo1p shares with mammalian linker histone H1 the ability to stabilize chromatin, as evidenced by the absence of Hmo1p or deletion of the Hmo1p CTD creating a more dynamic chromatin environment that is more sensitive to nuclease digestion and in which chromatin remodeling events associated with DNA double strand break repair occur faster; such chromatin stabilization requires the lysine-rich extension of Hmo1p. Further, my data indicates that Hmo1p functions in the DNA damage response by directing lesions towards the error-free pathway. My results suggest that Hmo1p controls DNA end resection and favors the classical non- homologous end joining (NHEJ) over alternate end Joining (A-EJ) that is error-prone process. In all, my study identifies a novel linker histone function of Hmo1p in Saccharomyces cerevisiae with the ability to stabilize genomic DNA, and appears to go beyond conventional linker histone function.
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Panday, Arvind, "Linker Histone Functions of HMO1- Implications for DNA repair" (2016). LSU Doctoral Dissertations. 4217.
Available for download on Saturday, February 23, 2019