The main goal of my research is to understand how chromatin structure affects chromosome segregation. For this purpose, we have undertaken genetic and molecular studies on the role that chromatin structure plays during the eukaryotic cell cycle, using the budding yeast Saccharomyces cerevisiae as model system. Our current work focuses on the role that histones, the core protein components of chromatin, have on centromere function. Since histones are among the most evolutionarily conserved proteins, studies in this simple and genetically tractable organism will be extremely valuable to understanding chromatin function in higher eukaryotes.
Current evidence indicates that histone H2A, one of the four histones that form the core of chromatin, is essential for normal centromere function. Mutations in this histone can result in mitotic chromosome loss as well as ploidy changes. These types of chromosomal changes are commonly present in cancer cells and can be devastating during mammalian development, giving rise to embryonic lethality and birth defects. It also appears that histones interact with previously unidentified cellular factors and that these interactions are required for normal chromosome segregation. We have identified and cloned the genes encoding some of these factors, and their functional characterization is underway. These studies will lead to a better understanding of the mechanisms by which histones and other factors control chromosome stability.
Mitotic chromosome segregation, chromosome stability, chromatin function, fungal genetics.
Ph.D. Louisiana State University Medical School, 1992.
Kanta, H., Laprade, L, Almutairi, A., and I. Pinto. 2006. Suppressor analysis of a histone defect identifies a new function for the Hda1 complex in chromosome segregation. Genetics 173:435-450.
Pinto, I. and F. Winston. 2000. Histone H2A is required for normal centromere function in Saccharomyces cerevisiae. EMBO J. 19 (7):1598-1612.
Wu, W-H, Pinto, I., Chen, B.-S. and M. Hampsey. 1999. Mutational analysis of yeast TFIIB: a functional relationship between Ssu72 and Sub1/Tsp1 defined by allele-specific interactions with TFIIB. Genetics 153:643-652.
Pinto, I., Wu, W-H., Na, J.G. and M. Hampsey. 1994. Characterization of sua7 mutations defines a domain of TFIIB involved in transcription start site selection in yeast. J. Biol. Chem. 269:30569-30573.
Pinto, I., Na, J.G., Sherman, F. and M. Hampsey. 1992. cis- and trans-acting suppressors of a translation initiation defect at the cyc1 locus of Saccharomyces cerevisiae. Genetics 132:97-112.