Cell cycle

What is the interphase

Long period of the cell cycle between one mitosis and the next. Includes G1 phase, S phase, and G2 phase

What are mitotic spindles

a giant bipolar array of microtubules formed in the centrosome 

• Made of microtubules 

• Abnormal when faulty M-cdk action (loss of phosphorylation) 

What is the restriction point

Important transition at the end of G1 in the eukaryotic cell cycle; passage past this point commits the cell to enter S phase. The term was originally used for this transition in the mammalian cell cycle; in this book we use the term “Start.”

What is a chromatid

condensed into pairs of rigid, compact rods 

What is the G1/G2 phase (overview)

Cell grow & “do their thing” 

G1 phase = APC/C and Cdk activation occurs and there is assembly of new prereplicative complexes at the origins. & the prereplicative complexes form at replication origins

What is the S phase

central event of chromosome duplication (DNA replication) Initiation of replication includes S-Cdk activation. Replication forks form. Elongation occurs. 

• Initiated in G1 (gathering all of the necessary proteins for replication – ORCs gather) 

• Must be copied accurately 

• Genome must be copied only once during the cycle (avoid gene amplification) 

• DNA replication initiates at origin of replication sites (DURING S phase) 

• Initiation of replication done in 2 steps (licensing & DNA pol. loading) 

What is the M phase (simple)

mitosis + cytokinesis 

What is a cyclosome

APC/C (cyclosome/anaphase promoting complex) 

• A ubiquitin ligase that catalyzes the destruction of major proteins like securin & S/M cyclins 

• Required for the completion of mitosis and beginning cytokinesis 

What is mitosis

Mitosis = copied chromosomes are distributed into a pair of daughter nuclei 

What is meiosis

Meiosis = the process through which an organism’s reproductive cells are formed 

What is recombination

only done in meiosis (switching between two sister strands)

What is a centromere

microtubule organizing center with embedded centrioles and nucleation site 

• Important during mitosis 

• Constricted region of a mitotic chromosome that holds sister chromatids together. This is also the site on the DNA where the kinetochore forms so as to capture microtubules from the mitotic spindle 

What is a kinetochore

large multilayered proteins built on heterochromatin at the centromere of a chromosome 

• Partly microtubules (has microtubules) 

• Various events occur with kinetochore microtubules finding kinetochores and motor proteins pushing and pulling (don’t attach to chr. But push and pull to drive things apart) 

• Chromosomes move along spindle assembly via motor proteins and possible depolymerization of microtubules 

What is condensin

Complex of proteins involved in chromosome condensation prior to mitosis. Target for M-Cdk. 

• Helps with condensation and keeping things organized 

• To avoid sister chromatid breakage (condensation (compaction of chromatids) and resolution (resolved into separable units) via condensin must occur) 

What is securin

Securin = Protein that binds to the protease separase and thereby prevents its cleavage of the protein linkages that hold sister chromatids together in early mitosis. Securin is destroyed at the metaphase-to-anaphase transition 

What are the 4 phases of the cell cycle (simple description)

Four phases:  

• M = M-Cdk activation occurs and chromosomes segregate 

• G1 (“Gap”) = the prereplicative complexes form at replication origins 

• S = DNA replication 

• G2 (“Gap”) = cell grow & “do their thing” (most active/gene expression) 

What are the 3 transition points of the cell cycle

Three transition points: is like a programmed timer that provides a fixed amount of time for the completion of each cell-cycle event (the way extracellular signals and cell size regulate progression with specific transitions/control points) 

• Cell cycle can be arrested at any point if the DNA is irreparably damaged or if the environment is unfavorable 

1. Start transition = cell commits to cell-cycle entry and chromosome duplication 

• Is the environment favorable to start the S phase

2. G2/M transition = early mitotic events with chromosome alignment on the spindle occur  

• Is ALL the DNA replicated and the environment is favorable to enter mitosis 

• DNA repaired as well 

3. Metaphase to Anaphase transition = sister chromatids separate, anaphase triggered 

• Are all chromosomes attached to the spindle to trigger anaphase and proceed to cytokinesis 

What are the stages of replication during the different steps of the cell cycle (DON’T LOOK AT THE IMAGE RN)

look at the image

What are cyclins

Cyclins = proteins that activate the Cdks (to do their thing) 

• Activated by specific cues 

  • Like cell size & intra/extracellular signals (growth factors/hormones) 

• Four classes = defined by the stage of the cell cycle at which they bind Cdks and function 

1. G1/S-cyclins (E) =

2. S-cyclins (A) = 

3. M-cyclins (B) =

4. G1 cyclins (D) =

What are the 4 cyclin types

Four classes = defined by the stage of the cell cycle at which they bind Cdks and function 

1. G1/S-cyclins (E) = activate Cdks in late G1 to trigger progression through the restriction point (commits to entry into cell cycle) 

2. S-cyclins (A) = bind Cdks to help stimulate chromosome replication and control early mitosis 

3. M-cyclins (B) = activate Cdks that stimulate entry into mitosis 

4. G1 cyclins (D) = govern activities of G1/S cyclins  

What are Cdks

Cyclin-dependent kinases = protein enzymes that add phosphates to various proteins involved in cell cycling 

• Phosphorylate things 

• Activity is regulated by its association with cyclins, activating & inhibitory phosphorylations, and binding of Cdk inhibitors 

Distinct pairs of cyclins and Cdks regulate progression through different stages of the cell cycle 

• Inhibitory mechanisms provide information about the extra- & intracellular environment 

• Cyclin-Cdk complexes are at the core of the control system 

What are the steps of replication initiation

1. During late mitosis and early G1, prereplication complex (pre-RC) assembles by ORCs (licensing) 

• M-cdk inhibits this step THEREFORE it occurs when cyclin M and Cdk1 is low 

• APC/C stimulates this step THEREFORE it happens when APC is high  

  • G1/S complex with high cyclin G1 

2. At onset of S phase, pre-RCs induce formation of preinitiation complex which unwinds the DNA helix and loads DNA polymerase 

• S-Cdk is activated and triggers preinitiation complex 

• Elevated S-Cdk keeps step 1 from happing again (until early G1) 

What is the pre-replication complex

Pre-replication complex = ORC + origin sequences on dsDNA + helicase + helicase loaders 

• Works because of low S-phase 

• S-Cdk presence and deconstruction of pre-RC bring on the pre-initiation complexes and phosphorylation of ORC (begin S phase) 

• Cdc6 and Cdt1 = helicase loading proteins 

What is the relationship between cyclin and Cdks during the cell cycle

look at image

What are the 5 stages of the M phase (described)

1. Prophase = the two DNA molecules are disentangled and condensed into sister chromatids, which remain linked by cohesion 

2. Prometaphase = starts abruptly with the breakdown of the nuclear envelope. Chromosomes can now attach to spindle microtubules via kinetochores and undergo active movement 

   • Nuclear evelope breakdown = must occur for sister chromatids to attach to spindle 

     • Complex, multistep process 

     • M-Cdk phosphorylates several subunits of nuclear pore complexes 

       1. Initiation of pore complex disassembly 

       2. Initiation of nuclear lamina (intermediate filament lamin) dissociation 

       3. Envelope broken into small vesicles 

3. Metaphase = Sister chromatids are attached to opposite poles of the spindle and align at the spindle equator in a stage 

4. Anaphase = segregation of chromosomes (2 independent yet overlapping processes) 

• The destruction of sister-chromatid cohesion at the start of anaphase separates the sister chromatids, which are pulled to opposite poles of the spindle 

Anaphase A = initial poleward movement of chromosomes 

Anaphase B = separation of spindle poles  

5. Telophase = 2 sets of chromosomes are packaged into daughter nuclei 

• The spindle is disassembled, and the segregated chromosomes are packaged into separate nuclei 

• Disassembly of the mitotic spindle 

• Re-formation of nuclear envelope by coalescing around chromosome clusters and re-formation of pore complexes (help from ER) 

• Contractile ring formation 

• Lots of dephosphorylation moves process backward  

What are the 2 phases in anaphase

Anaphase = segregation of chromosomes (2 independent yet overlapping processes) 

• The destruction of sister-chromatid cohesion at the start of anaphase separates the sister chromatids, which are pulled to opposite poles of the spindle 

Anaphase A = initial poleward movement of chromosomes 

Anaphase B = separation of spindle poles 

What is cytokinesis

Cytokinesis = cleaves the cell in two, so that each daughter cell inherits one of the two nuclei 

Chromatid separation = metaphase-to-anaphase transition initiated by APC 

• Cohesins disrupted by APC via securin and activated separase, allowing chromatids to separate 

  • APC activation unclear 

• S- and M-cyclins are destroyed and Cdks are inactived 

Describe the image

The activation of APC/C by Cdc20 leads to the ubiquitylation and destruction of securin, which normally holds separase in an inactive state. The destruction of securin allows separase to cleave Scc1, a subunit of the cohesin complex holding the sister chromatids together. The pulling forces of the mitotic spindle then pull the sister chromatids apart. In animal cells, phosphorylation by Cdks also inhibits separase. Thus Cdk inactivation in anaphase (resulting from cyclin destruction) also promotes separase activation by allowing its dephosphorylation. 

What is M-Cdk in spindle formation

M-Cdk = spindle formation 

• One single protein kinase complex, M-Cdk, controls all of the occurrences in early stages of mitosis 

• Cdk1 & cyclin M = M-Cdk 

• M-cdk phosphorylates key proteins 

  • Induces assembly of mitotic spindle in prophase 

  • Ensures sister chromatids are attached to opposite poles 

  • Triggers chromosome condensation (reorganization of intertwined sisters) 

  • Promotes breakdown of nuclear envelope 

  • Rearranges actin cytoskeleton 

How does mitotic spindle formation occur

Mitotic spindle formation  

Mitotic spindle formed in centromeres 

• Minus end of tubule is in the centrosome 

• Plus end extends away from the centrosome 

• Poles of spindles are within the centrosome 

How do motor proteins relate to MT (D/K)

Motor proteins important  

• Dynein walks toward the negative end of the microtubule 

• Kinesin walks towards the positive end of the microtubule 

 

What is mitosis? how is it different from meiosis

Mitosis = homologous chromosomes behave independently of each other (don’t line up together) 

• Only 1 round of anaphase and cytokinesis 

What is meiosis

Meiosis = chromosome duplication is followed by 2 rounds of chromosome segregation 

• Very important 

• DNA breaks are formed in each sister so they hold on to each other (crossover) = Homologous recombination  

• Critical for homologs to recognize each other and come together for meiosis I 

  • Homologos tightly connected and form chiasma (crosses)  

  • Crossing over is the basis of HR 

  • 2 rounds of anaphase and cytokinesis