The highly conserved N-terminal domains of histones H3 and H4 are required for normal cell cycle progression.
The N-terminal domains of the histones H3 and H4 are highly conserved throughout evolution. Mutant alleles deleted for these N-terminal domains were constructed in vitro and examined for function in vivo in Saccharomyces cerevisiae. Cells containing a single deletion allele of either histone H3 or histone H4 were viable. Deletion of the N-terminal domain of histone H4 caused cells to become sterile and temperature sensitive for growth. The normal cell cycle progression of these cells was also altered, as revealed by a major delay in progression through the G2 + M periods. Deletion of the N-terminal domain of histone H3 had only minor effects on mating and the temperature-sensitive growth of mutant cells. However, like the H4 mutant, the H3 mutants had a significant delay in completing the G2 + M periods of the division cycle. Double mutants containing N-terminal domain deletions of both histone H3 and histone H4 were inviable. The phenotypes of cells subject to this synthetic lethality suggest that the N-terminal domains are required for functions essential throughout the cell division cycle and provide genetic evidence that histones are randomly distributed during chromosome replication.
Morgan
B A
BA
Department of Microbiology, School of Medicine, University of Virginia, Charlottesville 22908.
Mittman
B A
BA
Smith
M M
MM
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D005075:Biological Evolution; D002453:Cell Cycle; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D006657:Histones / Q000235:genetics* / Q000502:physiology; D007700:Kinetics; D008969:Molecular Sequence Data; D010957:Plasmids; D016133:Polymerase Chain Reaction / Q000379:methods; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D012689:Sequence Homology, Nucleic Acid
D006657:Histones