GENETIC CONTROL OF CELL CYCLE ARREST AFTER DNA DAMAGE

Project: Research project

Description

In eucaryotes if chromosomes are damaged, the cell cycle arrests in G2,
just before mitosis and chromosome segregation. Genomic stability and
viability of eucaryotes requires controls that ensure mitosis does not
occur until chromosomes are intact. Arrest in G2 after DNA damage is
genetically regulated. The long-term objective of my research is to
understand how the cell detects DNA damage and signals arrest of the cell
cycle. In Saccharomyces cerevisiae, the mechanism of arrest in G2 requires
a negative regulator, the RAD9 gene. The genetic pathway controlling
arrest in G2 is complex; genetic analysis of mutants defective for arrest
in G2 show that 6 genes are essential for this regulatory control. My
research focuses on determining how the 6 genes for mitosis-entry
checkpoint, control cell cycle arrest after DNA damage. The MEC genes will be isolated and their DNA sequences determined to see it
they encode proteins of known biochemical or structural function. (DNA
sequence for two MEC genes has been completed). Genetic controls of
mitosis by the MEC genes may be complex and involve regulation of precesses
in addition to arrest in G2 after DNA damage; mec mutants will be examined
for a constitutive role in the transition from G2 to mitosis, for control
of DNA repair, and for regulation of arrest in other phases of the cell
cycle in addition to G2. Using the isolated MEC genes two genetic
approaches will examine epistasis and physical interactions of gene
products; a description of hierarchy of the MEC genetic pathway will
emerge. Additional MEC loci will be identified using a new genetic
selection, with a focus on genes that may be essential for mitosis and the
target of MEC-dependent control. Finally, the roles of three genes known
to be essential, or to regulate, mitosis will be tested genetically for
roles as possible targets or mediators of MEC-dependent negative control
(including CDC28, MIH1, and wee1).
StatusFinished
Effective start/end date1/1/9111/30/01

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $218,768.00
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Saccharomycetales
DNA damage
DNA Damage
mitosis
genes
Cell Cycle Checkpoints
Proteins
Genes
Mutation
eukaryotic cells
arrestins
Exonucleases
chromosomes
mutants
chromosome segregation
cell cycle checkpoints
epistasis
DNA repair
regulator genes
genetic techniques and protocols

ASJC

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)