Identifier

etd-10312016-222119

Degree

Doctor of Philosophy (PhD)

Department

Biological Sciences

Document Type

Dissertation

Abstract

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.

Date

2016

Document Availability at the Time of Submission

Secure the entire work for patent and/or proprietary purposes for a period of one year. Student has submitted appropriate documentation which states: During this period the copyright owner also agrees not to exercise her/his ownership rights, including public use in works, without prior authorization from LSU. At the end of the one year period, either we or LSU may request an automatic extension for one additional year. At the end of the one year secure period (or its extension, if such is requested), the work will be released for access worldwide.

Committee Chair

Grove, Anne

DOI

10.31390/gradschool_dissertations.4217

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Life Sciences Commons

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