Flashcards in MCM 2-12 Cell Division Deck (60)
what are the four phases of the cell cycle and brief description
G1 phase - Gap before DNA synthesis
S Phase - DNA synthesis phase
G2 Phase - Gap after DNA synthesis
M Phase - Mitosis
The gap before DNA synthesis. Cells in this phase have two copies of each chromosome (one copy of each homologue). It is the typical “resting” phase wherein general biosynthesis occurs. External signals (e.g. receptor activation-MAP kinase receptors) and internal state (e.g. cell size, DNA integrity) jointly influence whether a cell proceeds to division (S phase) or remain in G1 (G0 phase).
The DNA synthesis phase. Cells in this phase have an amount of DNA that gradually increases from that found in G1. During this phase histones and other proteins needed exclusively for DNA replication are produced. DNA is replicated from multiple replication origins (bidirectionally). After this is accomplished, the replication licensing factors are removed from the origin recognition complex to prevent re-replication. Centrioles duplicate but remain as a single centrosome (for now).
afterwards, replication "licensing factors" are removed from original recognition complex to prevent re-replication
The gap after DNA synthesis. Cells in this phase have four copies of each chromosome (two copies of each homologue). Proteins required for mitosis and cytokinesis are continued to be produced. Addition of cohesins links sister chromatids together, and addition of condensins combined with phosphorylation of histone H1 allows for chromosomes to condense at the beginning of M phase.
Mitosis. The onset of mitosis is controlled by kinase activity…the nuclear and cytoplasmic events are coordinated during the stages of mitosis largely through the actions of kinases and phosphatases that are active throughout the cytoplasm. Cells undergoing mitosis have four copies of each chromosome (two copies of each homologue) until cytokinesis. This phase is triggered by the activity of a cell-cycle regulatory kinase. Mitosis is further broken down into the following phases:
what are the major checkpoints controlling progression from one stage to the next?
G1/S border (start)
G2/M border (enter M)
Metaphase/anaphase transition (exit M) - tension on all kinetochores activates APC (an E3 ubiquitin kinase) targeting the mitotic cyclin and other proteins for destruction.
-Securin destruction releases separase to separate sister chromatids.
-Destruction of mitotic cyclin turns off Motitoc CDK.
describe mechanism of cyclin dependent kinase (CDK) Regulation
CDK's regulate cell cycle
complete CDK's (cyclin-CDK complexes) are composed of catlytic CDK subunit and regulatory (cyclin) subunit
-changes in cyclin concentration change CDK activity- the cell cycle is dependant upon this activity
-in order for an active cyclin-CDK complex to be formed, cyclin subunit must be synthesized and CDK (catalytic subunit) must be phosphorylated at one of two sites (one is inhibitory, one is activating).
when catalytic subunit is phosphorylated- both sites receive phosphase, keeping the subunit inactive. A phosphorylase then removes the inhibitory phosphate, activating the cyclin CDK complex
what are the kinases that phosphorylate CDK?
two different kinases are involved in phosphorylating the CDK's two sites
wee1 adds the inhibitory phosphate
cak (CDK activating kinase) adds the activating phosphate.
cdc25 removes the inhibitory phosphate to activate the complex
How are CDK's turned off?
by ubiquination. An E3 ubiquitin ligase tags the cyclin with polyunbiquitin chain, causing its degredation by the proteosome.
a phsophatase removes the activating phosphate.
describe the DNA damage repair pathway
p53 is major protein.
in response to DNA damage, protein kinases are activated that phosphorylate P53, stabilizing/activating it
active p53 binds to regulatory regions of small inhibitory protein genes leading to the synthesis of the small inhibitory proteins that inhibit active CDK's. This arrests the cell cycle in whichever phase it is in.
protein produced depends on phase of the cell cycole which the damage is detected.
During G1/S checkpoint, if damage is detected, p53 upregulated the gene p21, which leads to synthesis of the protein p21; it inhibits G1/S- and S-CDK's
4 basic goals of cell division
approximate doubling in volume and content
exact duplication of genome
exact segregation of duplicated genomes
division into 2 new cells,
each toerh approximate equal volumes/content and 1 genome per copy
describe G1, S, G2, and M in terms of chromosome number
G1 - cell growing but dna not replicating, 2n
S - dna syntehsis. from 2 to 4n
G2 - 4n cells
mitosis - reduction of 4n into 2 2n cells
what phase is this?
typical resting phase
general biosynthesis occurs (growth/maintenance)
what influences the movement from G1 to S
external - receptor mediated pathways (growth factors, hormones, MAP kinase)
Internal - look at internal state, must have accumulated enough "stuff", enough nutrition, decides its big enough to divide
What events occur during S phase
Duplicating DNA, means you must also duplicate histones
-synthesizing nezymes required for DNA replication
-DNA replication occurs at multiple origines
-removal of replication licensing factors (via the phosphorylation of cdc6 by s-CDK)
centrioles duplicate, but do not separate until mitosis
why is S-phase unidirectional?
because you destroy the replication licensing factors (cdc6) that recongie origin. must wait until cell cycle ends to make more.
continued syntehsis of proteins required for mitosis and cytokinesis
addition of cohesins links sister chromatids
once condensins and histones are phosphorylation, enters into Mitosis prophase
Mitosis - Prophase
defined by chromosomes condensing and 2 centrosomes separating.
KEY - still has nuclear membrane. This defines prophase.
1. chromosomes condense
2. spindle forms (duplicated chromosomes separate)
3. kinetochores (proteins) assemble on the centromeric portion of DNA
what markes transition from Mitosis prophase to prometaphase?
breakdown of nuclear envelope by the phorphorylation of lamins which is a function of CDK (cyclin dependant kinase)
what triggers mitosis?
activity of a cell-cycle regulatory kinase
after nuclear envelope breakdown
-allows microtubules radiating from centrosomes to be captured by the kinetochores, forcing chromosome pair to middle of cell
defining feature - all chromosomes attatched to both sides and lined up on metaphase plate.
Once lined up, kinetochore cascade gets turned off (if cascade on, wont proceed).
describe the balanced forces during metaphase
tension on kinetochore fibers pull inward, balanced by outward forces of overlapping polar microtubules being pulled in opposite directions by kinesin
tension on kinetochores activates the Anaphase Promoting Complex (APC) that triggers destruction of coheins (which keep sister chromtids togetner).
Chromatids separate and move towards opposite poles (anaphase)
anaphase can be broken down into two types of movement
1. A - microtubules get shorter, the kinetochores chew the microtubules, puling the chromatids towards the poles
2. B - kinesins continue to actively push the poles apart on the bipolar microtubule arrays, furhter separating and elongating the cell.
finish dividing cell by forming ring of actin filaments (non-muscle myosin 2)
-spindle disassembles, ring assembles via signals sent at middle of spindle.
chromosomes decondense via phosphatase activity reversing effects of mitotic kinase on the chromosomes (causing condensation)
prepares for cytokinesis
contractile ring of antiparellel microfilaments associated with cell membrane and non-muscle myosin II. Similar to belt junction, constricts the cell
orientation of mitosis apparatus determines position of contractile ring
what does cell lose during mitosis and cytokinesis?
cells lose adhesion and round up
cells that fail to complete cytokinesis...
cells that fail to complete mitosis...
polyploid - multiple copies of genome in one nucleus