Mitosis and Cell Cycle II Flashcards
Cell Cycle checkpoints
Checkpoints are surveillance mechanisms that monitor cell cycle events.
For example, if the DNA made in S phase is damaged, the DNA damage checkpoint will block entry into mitosis until the damage is repaired.
If the mitotic spindle is damaged, then the mitotic checkpoint will block exit from mitosis until the spindle is repaired.
Checkpoints prevent aneuploidy, in which there are too few or too many chromosomes. Aneuploidy can produce many diseases including cancer and birth defects.
DNA checkpoint regulation
Usually occurs by activation of specific enzymes that modify and inhibit proteins needed for cell cycle progression.
In the DNA damage checkpoint, CDK cyclin complexes are inhibited by p53 and Chk2.
Patients with Li Fraumeni syndrome have a high risk for cancer and have mutated p53 or Chk2 gene. The idea is that these patients accumulate many mutations leading to cancer.
ATM and ATR
these two protein kinases are integral components of the DNA damage checkpoint.
Like with Li Fraumeni syndrome, patients that lack ATM have a high risk of cancer, but unlike also have Li Fraumeni, they also have neurological defects (Ataxia=poor coordination of movements; Telangiectasia=small dilated blood vessels).
BRCA1 and BRCA2 mutations
have a high risk for breast and ovarian cancer. Their cells are also checkpoint defective giving rise to genomic instability and a high risk for breast cancer because BRCA1 and BRCA2 proteins regulate the ATM/ATR checkpoint pathway.
In these patients DNA damage is not recognized and repaired properly resulting in chromosome breakage and abnormal recombination events. This is referred to as a “genomic instability” phenotype.
Meiosis vs. mitosis
The goal of the meiotic cell cycle, which occurs only in germ-line cells, is to produce haploid gamete cells. There are two divisions after DNA replication. Meiosis I, in which the homologues separate (a reductional division), followed by Meiosis II, in which the replicated sister chromosomes separate (an equational division like mitosis). In males, this results in sperm and in females, immature eggs called oocytes.
Rad17 etc.
Rad17 –> ATR –> chk 1/2 activating repair enzymes —> and BRCA1/p53
ATM–> p53 –> p21 leading to arrest or apoptosis or DNA repair
Checkpoint G2
Correct copies of old/new DNA?
checkpoint at M?
Did spindles form and act as they should have?
p16 and p21
p16 (INK4) inhibits CDK4/5, preventing passage to S phase
p21 (cip and kip)
inhibits CDK2 by preventing activation of synthesis (S phase)
