Date of Graduation
7-2026
Document Type
Dissertation
Degree Name
Doctor of Philosophy in Cell & Molecular Biology (PhD)
Degree Level
Graduate
Department
Cell & Molecular Biology
Advisor/Mentor
Pinto, Inés
Committee Member
Lewis, Jeffrey
Second Committee Member
Ivey, Mack
Third Committee Member
Egan, Martin
Keywords
Chromatin remodeling; Chromosome segregation; Genome integrity; Histone variants; Ploidy maintenance; Saccharomyces cerevisiae
Abstract
Just as cells are termed building blocks of life, nucleosomes serve as building blocks of chromatin. Chromatin is responsible for maintaining the integrity of the genome through super compaction of large DNA molecules in a tiny nuclear space of a cell. To do this, organisms pack their DNA in a particular set of chromosomes which vary from organism to organism. Ploidy denotes this varying number of total set of chromosomes of an organism. Thus, DNA replication and faithful chromosome segregation direct proper flow of genetic material as well as maintain proper ploidy. Maintaining ploidy is necessary to prevent aneuploidy (loss or gain of chromosomes) and polyploidy (gaining an extra set of total chromosomes) which could lead to a host of different genetic abnormalities including cancer. Apart from the well-known roles of nucleosomal histone and nonhistone proteins, the role of chromatin remodeling complexes in maintaining ploidy and chromosome segregation has recently begun to emerge. Here we show that two such ATP dependent chromatin remodelers INO80 and SWR1 play important role in maintaining proper ploidy and genomic integrity. A screen of the S. cerevisiae non-essential deletion library in our lab for genes involved in segregation revealed that some subunits from both complexes are involved in faithful chromosome segregation in addition to their well-established roles in DNA replication and repair. Both INO80 and SWR1 are multisubunit complexes, comprised of 15 and 14 subunits respectively, and specific contribution of their subunits in chromosome segregation remains unknown, for the most part. The INO80 complex has been shown to be involved in ploidy maintenance through its Ies6 and Ino80 subunits (Chambers et al. 2012), which result in ploidy increase. The SWR1 complex catalyzes the exchange of H2A for H2A.Z (Htz1 in yeast) while INO80 complex removes H2A.Z from nucleosomes. Here we show a correlation between chromosome missegregation and H2A.Z turnover in the subunit mutants of both complexes, implicated to be involved in chromosome segregation in the initial screening. Our study shows that only the catalytic subunits and a few other subunits, but not all, of both complexes are required for faithful chromosome segregation and ploidy maintenance.
Citation
Hossain, M. (2026). Involvement of INO80 and SWR1 Chromatin Remodelers in Ploidy and Genome Integrity in Saccharomyces cerevisiae. Graduate Theses and Dissertations Retrieved from https://scholarworks.uark.edu/etd/6387
