What are the four phases of the cell cycle?
(each phase requires the completion of the previous phase)
What happens in G1 phase of the cell cycle?
G1 is the first growth phase, when the cell grows and synthesize proteins need for DNA replication
What happens in S phase of the cell cycle?
S phase is the DNA synthesis phase, when DNA replication occurs
What happens in G2 phase of the cell cycle?
G2 is the second growth phase, when the cells synthesize proteins needed for mitosis.
What happens in M phase of the cell cycle?
M is the mitotic phase, when the cell undergoes mitosis, the process of segregating the replicated DNA (in the from of duplicated chromosomes)
What is interphase in the cell cycle?
Interphase is G1, S, and G2 combined, it is the period between success mitoses.
What are the phases of mitosis?
Prophase, Metaphase, Anaphase, Telophase, Cytokinesis
What happens during prophase of mitosis?
During prophase, the chromosones codense, mitotic spindles forms between two centrosomes as they move to opposite ends of the cell. Organelles disassemble
What happens during metaphase of mitosis?
During metaphase, chromosomes finish attaching to the spindle and line up at the center of the cell.
What happens during anaphase of mitosis?
During anaphase, sister chromatids separate from each other and are pulled towards opposite ends fo the cell
What happens during telophase of mitosis?
During telophase, mitotic spindle break down, two nuclei form, chromosomes decondense, organelles reassemble
What happens during cytokinesis of mitosis?
During cytokinesis, the division of the cytoplasm to form new cells, this starts in late anaphase and finishes shortly after telophase
What are the differences in Meiosis?
Meiosis halves chromosomes, there is synapsis of homologous chromosomes, and crossing over occurs only in Meiosis.
What are the differences in Mitosis?
Mitosis divides chromosomes equally, results in diploid cells, there is one round of replication and one round of nuclear division
What are the similarities between mitosis and meiosis?
They both occur in stages, there is an S phase in both, sister chromatids line up at the metaphase plate
What are the results of mitosis?
Mitosis results in one cell division, results in 2 diploid daugher cells, daughter cells are genetically identical, creates all body (somatic) cells except germ cells
What are the results of meiosis?
Meiosis results in two cell divisions, results in 4 haploid daughter cells, daughter cells are genetically different, creates germ cells (eggs and sperm)
What are cyclin/cyclin-dependent kinase complexes?
Cyclin-CDK are holoenzymes that regulate the cell cycle, controlling passage between phases. Cyclins are thee rgulatory subunits of the complex. Different cyclin family members are expressed druing certain cell cycle phases (cyclins A,B,D,E). The cyclins bind to CDKs, the catalytic subunit. CDK1, CDK2, CDK4, CDK6 are serine/threonine kinases and are only active when bound to cyclin
What does Cyclin D bind to and what phase does it regulate?
Cyclin D binds either CDK4 or CDK6 (cell type specific) to regulate G1 phase
What does Cyclin E bind to and what phase does it regulate?
Cyclin E binds to CDK2 to regulate the transiton from G1 into S phase (the beginning of DNA replication)
When Cyclin A binds to CDK2, what does it regulate?
Cyclin A binds to CDK2 to regulate S phase (DNA replication)
When Cyclin A binds to CDK1, what does it regulate
Cyclin A binds to CDK1 to regulate entry into mitosis
What does Cyclin B bind to and what does it regulate?
Cyclin B binds to CDK1 to regulate mitosis
What are the four mechanisms that regulate cyclin-CDK complexes?
(1) Cyclin binding activates CDK (2) Phosphorylation of the CDK can inhibit or activate its kinase activity (3) CDK inhibitors (CKIs) can bind cyclin/CDK complexes to sertically inhibit their activity (4) Proteolysis of cyclins inhibit CDK activity and proteolysis of CDK inhibitors activates CDK activity
What are CKIs and what are the important ones?
CKI can bind cyclin/CDK complexes to sterically inhibit their activity; the ones that bind multiple complex are called the CDKN1 **p21**; CKIs that bind and inhibit only CDK4/6 are called the CDKN2 family ***p16***
What are the important checkpoints in the cell cycle?
The important check points in the cell cycle are the restriction checkpoint, DNA damage checkpoints, and the mitotic or spindle assembly checkpoint. These checkpoints act primarily by inhibiting cyclin-CDK complexes to halt cell cycle progression until the problem is solved and if not the cell will undergo apoptosis.
What happens during the restriction point?
The restriction point happens in G1, it is defined as the point after which the cell cycle will proceed even ift the growth factors are withdrawn. The cell commits to replicating DNA once it passes the restriciton point.
What protein controls the restriction point?
The restriction point is controlled by retinoblastoma protein, Rb.
How does Rb control the G1 restriction point?
In the presence of growth factors that elicit cyclin D via upregulation of myc, cyclin D binds and activates CDK4/6, D-CDK4/6 hyperphosphorylates Rb which inactivates it letting go of E2F. E2F then activates transcriptoin of S phase genes including Cylcin E. Cylcin E/CDK2 also phosphorylate Rb ensuring inactivation as well as transcription of other S phase genes.
When is Rb active?
Rb is active when it is less phosphorylated, it will hold on to E2F and block transcription of S phase genes.
When is Rb inactive?
Rb is inactive when it is hyperphosphorylated by D-CDK4/6, then it lets go of E2F which allows for transcripton of S phase genes.
How is D-CDK4/6 inhibited?
It can be inhibited by several growth inhibitors such as p53 which stiluate p16 and p16 will inactivate D-CDK4/6 and not allow Rb to be phosphorylated, Rb remains active (holds on to E2F) and does not allow for S phase gene transcription.
When do the DNA damage checkpoints occur?
DNA damag checkpoints occure at G1/S transition, G2/M transition and S phase.
How are DNA damage checkpoints signaled?
DNA damage (ds breaks, mismatched, nucleotide damage, stalled replication forks) activate ATM or AR kinases. ATM/AR phosphorylate and activate the checkpoint kinases (Chk1 or Ch2). Chk1/2 activation can result in repair of the the DNA, phosphorylate Cdc25 which inhibits CDKs, phosphorylate p53, a tumor suppressor. p53 is a transcription factor that can initiate apoptosis if DNA damage cannot be repaired or cell cylce arrest via upregulation of the CDK inhitior p21.
What happens during the mitotic or spindle asemble checkpoint?
This M checkpoint senses chromosomes not attached to the mitotic spindle during mitosis, and arrests cells at metaphase. The checkpoint halst the metaphase to anaphase transition to prevent errors in sister chroamtid separation.
What happens when a chromosome is nto attached to a mitotic spindle?
A protein called mitotic arrest deficient 2 (Mad2) is recruited to the kinetochore (the region where the microtubles fo the spind bind to the chromsome). Mad2 then binds to and inhibits a ubiquitin ligase called the anaphase promoting complex, APC. The APC/C is responsible for tagging mitotic proteins with ubiquit chains, thus trageting them for degradation by the 26S proteasome. One of these proteins is securin, which helps maintain the sister chromatids cohesion until all the chromsomes are lined up at the metaphase plate. As long as Mad2 is bound to the kinetochore of the chromose then APC/C is inhibited and the cell cannot complete transiton to anaphase. If a microbuble binds to the kinetochore, it displaces Mad2, the chromosomes line up at the metaphase plate and the cell completes its devions.
What is the difference between oncogenes and tumor suppressors?