Cell Cycle Flashcards
Basic Goals of Cell Division
- approximate doubling in volume of content
- exact duplication of genome
- exact segregation of duplicated genomes
- division into two new cells, each with approx equal volumes/content and one complete genome copy
Phases of cell cycle
G1, S, G2, M
G1
gap before DNA synthesis (2N DNA/cell)
S
DNA synthesis (gradually increasing DNA/cell)
G2
gap after DNA synthesis (4N DNA/cell)
M
mitosis (4N DNA/cell until cytokinesis)
Alternatives to cell division
polyploidy, multinucleation
Regulation of Cell Cycle
Cyclin dependent kinases and checkpoints: Times when the cell monitors specific activities before proceeding to the next cell cycle stage.
Occur at:
G1/S-enter S or Start
G2/M- enter M
Metaphase/Anapahse transistion in M (Exit M)
Cyclin-Dependent Kinases
regulators of cell cycle progression. consist of catalytic subunit and regulatory subunit. (CdK +cyclin) they are inactivated until phosphorylated when indicated.
- S-CDk once activated turns on DNA replication machinery
- M-CDk turns on mitosis when activated and when turned off completes mitosis (last checkpoint)
G1
Typical “resting” phase
General biosynthesis (growth maintenance)
External signals and internal state combine to make decision to remain in G1 or divide (proceed to S)
External signals: receptor activation
Internal state: size, DNA integrity
S Phase
- Histone synthesis
- Synthesis of enzymes required for DNA replication
- Replication of DNA from multiple Replication Origins
- Removal of replication licensing factors from ORC prevents re-replication until next cell cycle. CDC6 is on ORC (signalling it’s ready), becomes phosphorylated, comes off so replication can start, and isnt put back on until next cycle
- Duplication of centrioles (but centrosomes don’t duplicate until M phase)
G2
- continued synthesis of proteins required for mitosis and cytokinesis, including the cyclin for the cdk that regulates entry into M phase.
- DNA repair checkpoint activity
- Addition of cohesins to link sister chromatids, Condensins are added in mitosis
Mitosis-Prophase
chromosomes condense, spindle forms, kinetochore assemble.
astral MT add stability
Kinesin motors crosslink some MT and aid in elongation
Mitosis-Prometaphase
- nuclear envelope breakdown (lamin phosphorylation)
- spindle invades nucleus
- kinetochores capture MT
Nuclear Envelope Breakdown (NEB)
Phosphorylation of lamin IF subunits by mitoticcdk leads to breakdown, which is the start of prometaphase
Kinectochores and MT
capture the MT and support bidirectional movement of chromosomes.
Bipolar attachment
need attachment of chromosomes to spindle on both sides. results in tension on the spindle poles and allow chromosomes to line up at the metaphase plate. cannot continue to anaphase until biopolar attachment on all chromosomes
-balanced forces prevent collapse. kinetochores pull in and overlapping MT push out
Metaphase/Anaphase Checkpoint
controlled by kinase activity. tension on kinetochores (by bipolar attachment) inhibits the kinase, turns on phosphatase, dephosphorylates mcdk, and allows anaphase
Anaphase Promoting Complex
triggered by the phosphatase- destructs cyclin subunits (keeping in metaphase) and cohesions. chromatids can then separate since mcdk is off-trigger anaphase
Metaphase
chromosomes are aligned at the equator of the spindle, kinetochore MT are attached
Anaphase
- separation of sister chromatids
- two types of movement- chromosome to pole (kinetochore) and pole/pole separation (kinesins on MT).
Telophase
reformation of the nucleus. phosphatase reverses the effects of mcdk during anaphase and telophase
spindle is disassembled, nucleus reassembles
prep for cytokinesis
Cytokinesis
- contractile ring of antiparallel microfilaments associated with the cell membrane and non-muscle myosin II constricts the cell
- orientation of mitotic apparatus determines the position of the contractile ring (perpendicular)
Mitosis and Cytokinesis
not always linked: cells lose adhesion and roundup during mitosis and cytokinesis can become: -binucleate -polyploid -undergo apoptosis