Lecture 16: Cell Cyle Checkpoints Flashcards
The events that take place during different phases of the cell cycle must be
coordinated with one another so that they occur in the appropriate order, the order is also preserved even if one event takes longer than usual.
It is critically important that the cell not begin M phase until
DNA replication during S phase is completed, if not completed cell division is destroyed as the daughter cells wont inherit complete copies of daughter chromosomes.
Why is it crucial for cells to double in size during interphase before diving into two during M phase?
because cells would get smaller with each division, thus daughter cells are too small.
The coordination between different events of the cell cycle is achieved by
a system of checkpoints (STOPS).
What do checkpoints prevent?
They prevent entry into the next phase until the events in preceding phase are finished.
Distinguish G1 checkpoint #1 and #2
#1: beginning of G1 phase, asks if nutrients and/or growth factors available. #2: end of G1 phase, asks if DNA is damaged.
Distinguish G2 checkpoint #1 and #2
#1: beginning of G2 phase, asks if all DNA is replicated. #2: end of G2 phase, asks if the cell is big enough.
Distinguish Anaphase checkpoint # 1 and #2
#1: do all chromosomes align at the metaphase plate. #2: is the mitotic spindle assembled properly.
Define G1 DNA damage arrest
allows repair of the damage to take place before the cell enters S phase.
Steps in G1 DNA damage arrest
Step 1: DNA damage increases the conc and activity of gene regulatory protein p53 (low conc=inactive, high conc= active).
Step 2: activated p53 binds to regulatory region of p21 gene encoding an S phase Cdk inhibitor protein, stimulating the transcription of p21 gene thus increasing conc of S phase Cdk inhibitor protein p21.
Step 3: p21 protein binds to “cyclin A -S phase Cdk” complex and inactivates it, so that the cell cycle arrests in G1 phase, allowing time to repair the DNA damage before its replicated.
In which disease is the gene encoding p53 mutated?
In cancer, damaged DNA continues to be replicated leading to increase in mutations, produce cell that become cancerous.
How can cells disassemble their cell control system?
animal cell cycle is regulated by extracellular growth factors that promote cell division, if their are no growth factors the cell cycle arrests at a G1 checkpoint called the restriction point. Now the cell enters a stage called G zero where they stay for long a long time without dividing, Cdks and cyclins disappear. Cells stay in G zero until growth factors come.
Describe the arrest in skin fibroblasts
Skin fibroblasts are arrested in G zero until they are stimulated by a growth factor to divide, required to repair damage from a wound.
In yeast cells the passage through a G1 check point called the
START point.
The cell cycle arrest at the START point for yeast cells if they are
deprived of nutrients, exposed to mating factors, or not big enough.
Chromosomal DNA must be replicated how many times during one cell cycle?
once per cycle.
Once DNA is replicated once control mechanisms prevent cells in G2 phase from re-entering S phase (T/F)
True, by blocking another round of DNA replication until G1 phase of next cycle with G2 checkpoint that stops it.
Steps in restriction of DNA replication to once per cell cycle by the MCM protein complex
Step 1: in G1 phase MCM complex with ORC (origin replication complex) binds to origins of replication, required for the initiation of DNA replication. MCM only available to bind to DNA in G1 phase.
Step 2: In the S phase, the MCM complex is removed from DNA and in turn binds geminin (protein whose synthesis is initiated in S phase), which prevents the re-binding of MCM to DNA.
Step 3: when the cell completes mitosis, geminin is degraded so that MCM can once again initiate replication during the next cell cycle.
