Gcn5p plays an important role in centromere kinetochore function in budding yeast.
We report that the histone acetyltransferase Gcn5p is involved in cell cycle progression, whereas its absence induces several mitotic defects, including inefficient nuclear division, chromosome loss, delayed G(2) progression, and spindle elongation. The fidelity of chromosome segregation is finely regulated by the close interplay between the centromere and the kinetochore, a protein complex hierarchically assembled in the centromeric DNA region, while disruption of GCN5 in mutants of inner components results in sick phenotype. These synthetic interactions involving the ADA complex lay the genetic basis for the critical role of Gcn5p in kinetochore assembly and function. We found that Gcn5p is, in fact, physically linked to the centromere, where it affects the structure of the variant centromeric nucleosome. Our findings offer a key insight into a Gcn5p-dependent epigenetic regulation at centromere/kinetochore in mitosis.
Istituto di Biologia e Patologia Molecolari, CNR, c/o Dip. Genetica e Biologia Molecolare, Sapienza Università di Roma, P. le A. Moro 5, 00185 Rome, Italy.
Stefano
S
Vernarecci
Prisca
P
Ornaghi
Anacristina
A
Bâgu
Enrico
E
Cundari
Paola
P
Ballario
Patrizia
P
Filetici
D048868:Adaptor Proteins, Signal Transducing; D002453:Cell Cycle; D002503:Centromere / Q000648:ultrastructure*; D051548:Histone Acetyltransferases / Q000502:physiology*; D018386:Kinetochores / Q000502:physiology*; D008938:Mitosis; D046912:Multiprotein Complexes / Q000502:physiology; D009707:Nucleosomes; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000166:cytology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism* / Q000502:physiology; D000099224:p300-CBP-Associated Factor
D048868:Adaptor Proteins, Signal Transducing; D051548:Histone Acetyltransferases; D046912:Multiprotein Complexes; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; C106162:HFI1 protein, S cerevisiae; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor