HAT Gcn5p is
required for proper chromosome segregation and mitotic exit.
Patrizia Filetici (1), Enrico Cundari (1), Emanuela De Cinti (2), Roberta Morisi
(2), Prisca Ornaghi (2), Enzo Marchetti (2), Paola Ballario (2)
(1) IBPM, CNR, c/o Dept. Genetica e Biologia Molecolare, Università La
Sapienza, P.le A.Moro 5, 00185 Roma-Italy (patrizia.filetici@uniroma1.it); (2)
Dept. Genetica e Biol. Molecolare, Università La Sapienza, P.le A.Moro 5, 00185
Roma-Italy
Chromatin acetylation and nucleosome remodeling regulate the DNA accessibility to factors and complexes involved in different cell functions. The histone acetyltransferase Gcn5p is not only a pleiotropic coactivator of aminoacid biosynthetic genes but also of a subset of genes required for mytosis exit. In order to investigate when and how Gcn5p elicits its function in cell cycle control we have detailed the phenotypic defects of a Δ-gcn5 strain in different conditions. Our experimental evidences showed that, beside a large proportion of slowly growing G2 cells, Δ-gcn5 presented peculiar mitosis exit phenotype. Defective nuclear migration into the daughter cell and unelongated spindles were observed in ayncronously growing cell population. Time laps experiments uncovering cell division were performed to visualize the dynamics of spindle elongation with GFP-tubulin by confocal microscopy. Spindle in Δ-gcn5 was short and unable to migrate into already septated daughter cell. In addition, elevated chromosome loss in disrupted gcn5 strain and an altered MNase accessibility of bulk chromatin organization suggested an interdependence of chromatin structure, Gcn5p function and the spindle checkpoint pathway. In order to distinguish if the observed defects deal with an abnormal chromosome attachment to microtubules or with the spindle misorientation within the cytoplasm we have approached the study of double mutants in spindle check point proteins.