Palmer- Physiology- Exam 3 worksheets 14-15

Whare are the 4 major events that occur before and during cell division?

1. Reproductive signal

2. Replication of DNA

3. Segregation

4.Cytokinesis

What is the reproductive signal?

A signal to reproduce is received to initiate cell division

Growth Factor or Growth hormone!

What is cell segregation?

DNA is distributed to new cells (Mitosis/ Meiosis)

What is the major difference between meiosis and mitosis

Mitosis- division of somatic (body) cells. Create identical copies.

Meiosis- division of germ-line (sex) cells. create non-identical copies

which creates genetic diversity? Mitosis or meiosis?

Meiosis

What are the 2 stages of the cell cycle?

Mitosis (M- Phase)

Interphase

What is happening in M phase

the cell undergoes all stages of Mitosis and Cytokinesis, resulting in two new cells.

active dividing

Describe what is happening in each phase of interphase

G1 (Gap 1)- happens just after mitosis and before DNA synthesis. DNA is unreplicated. variable timeline

S Phase (Synthesis)- Cell' DNA is replicated, DNA synthesis

G2 (Gap 2)- DNA is duplicated at this point, cell makes preparations for mitosis like making microtubules for mitotic spindle

What 2 types of signaling molecules are used to stimulate cell division?

name examples

Growth Factors- ex: EPO, interleukins

Hormones- ex: Estrogen

Which type of pathway does EPO use to signal RBCs to mature and divide?

JAK/STAT pathway,

What types of pathway do interleukins use to stimulate transcription/translation of target genes?

JAK/STAT pathway, Ras activation and PI3K pathway

what type of pathway does estrogen use and what does it stimulate

steroid hormone superfamily of receptors and stimulates transcription

The events in DNA replication are ...?

a. Helicase - 'Unzips' the double helix allowing the parental strands to be exposed for copying

.b. DNA gyrase (topoisomerase) - removes supercoiling caused by helicase.

c. Single stranded binding proteins - prevent separated DNA from reannealing (rewinding), stabilizing the replication fork.

d. Primase - produces a short RNA primer, made of ribonucleotides, so that DNA polymerase can recognize where to start copying the strands.

e. DNA polymerase III - adds deoxyribonucleotides to the 3' end of the growing daughter strands

.f. DNA polymerase I - removes the RNA primers replacing them with the appropriate DNA nucleotides according to base pairing rules. Also plays a role in some DNA repair mechanisms.

g. Ligase - forms the phosphodiester bonds to seal the 'gaps' after the removal of the primers.

what phase of the cell cycle does DNA replication take place?

S phase

What are the structures of a duplicated chromosome

Duplicated Chromosome= 2 sister chromatids held together at the centromere.

Each sister chromatid is made of Chromatin

What does chromatin include?

proteins and DNA that make up sister chromatids

How many chromosomes do humans have?

46 (23 pairs)

When does DNA start to get packed into chromosomes

Begins in G2 of Interphase but not complete until prophase of mitosis

Explain the structure of a nucleosome and its parts

DNA wrapped around histones

Contains: 8 histone molecules, 146 base pairs of DNA and an H1 linker histone

What are the 5 classes of histone proteins?

H1, H2A, H2B, H3, H4

*H1 is a linker histone!

What histone modification could I make if I wanted to increase the transcription of a gene? enzyme used?

Acetylation!

Histone acetyl transferases (HATs) add acetyl group to lysine residues and weakens DNA histone interactions, allowing more transcription

To decrease gene transcription, what histone modification would you make? enzyme used?

Remove an acetyl group

Histone deacetylases (HDACs) remove acetyl group making DNA and histone interaction tighter, resulting is decreased transcription

What is the difference between euchromatic and heterochromatin

euchromatin- "active DNA" genes are available to be transcribed. They are not wrapped tightly around a histone

heterochromatin- "DNA is inactive" and tightly condensed around a histone/

what phase of the cell cycle do the centrosomes replicate?

When do they move to opposite cell poles?

Replicated in S-phase

separate and move to opposite ends in G2-M transition

what is the most important structure in cell division?

mitotic spindle

What is the difference between the centromeres and the centrioles

Centromeres: region of the chromosome where spindle fibers attach via kinetochore proteins

Centrioles: two cylindrical cellular structures that are composed of nine triplet microtubules and form mitotic spindles.

what is the centrosome?

region where microtubules form, each produces 2 centrioles

What cytoskeletal protein makes the mitotic spindle?

What structure does it arise from

microtubules

the centrioles

What is the difference between the polar and kinetochore microtubules?

polar microtubules: form framework of the spindle. overlap and interact with a microtubule from other side

Kinetochore microtubules: attach to kinetochores on chromosomes

What is a kinetochore and where is it located

Where the kinetochore microtubules attach to the centromere of the duplicated chromosomes.

What happens in prophase

- Chromosomes condense

- DNA has been duplicated in S phase

-mitotic spindle develops

-Nucleolus disappears

What happens in Metaphse

- All centromeres at at the equatorial plate

- chromatids are now clearly connected to the poles by microtubules

What happens in anaphase

- separation of the chromatids toward the opposite ends of the spindle

-happens from kinetochore microtubules shortening

What happens in telophase

- disassembly of the mitotic spindle

- nuclear envelopes re-form and the chromosomes decondense

nucleolus will also reform in daughter cells

what happens in prometaphase?

sister chromatids become attached to the kinetochore (strandy part of the spindle), which are attached to the centrsome, part where nuclear envelope breaks

What are the 5 types of chromosomal mutations?

1. Nondisjunction

2. Deletions

3. Duplications

4. Inversions

5. Translocations

What happens in chromosomal nondisjunction

causes too many or too few chromosomes due to chromosomes failing to separate during anaphase

What happens in chromosomal deletions

segment of chromosome is removed

what happens in chromosomal duplication

chromosomal segment is doubled

what happens in chromosomal inversions

when a chromosomal segment is reattached upside down

what happens during chromosomal translocations?

when a segment is swapped with another chromosome segment

what phase of cell division does nondisjunction occur in?

anaphase

What phase of cell division does deletions, duplications, inversion and translocation all occur in?

during crossover in prophase 1 of meiosis 1

What are the phases of the cell cycle?

G1, S, G2, M

What is G0 and why would a cell enter this phase?

specialized resting phase

cells exit the cell cycle and pause division due to lack of nutrients

What is happening during mitosis

cells are actively dividing (PMAT-C)

Why are cell cycle checkpoints important?

ensures that the cell is healthy and has all components needed for proper division

What is being assessed at a cell cycle checkpoint?

- DNA and organelles are properly replicated

- no DNA mutations

- Chromosomes have attached to spindle fibers/properly separated during anaphase

What is the difference between phosphorylation and dephosphorylation?

What class of enzymes is used for each?

Phosphorylation is the addition of a phosphate group to a substrate.

Dephosphorylation is the removal of phosphate groups from a substrate

What are cyclins

proteins that CDKs are dependent on.

produced only in response to signals like growth factors and hormones

What are cyclin-dependent kinases?

specific protein kinases that trigger transitions from phase to phase in the cell cycle.

they are always present but not always active

how does the process of cyclins and CDKs work?

1. CDK is activated by binding to a cyclin, altering protein shape (exposing active site)

2. Cyclin-CDK complex acts as a protein kinase to phosphorylate regulatory proteins- triggering phase transition

3. Cyclin then breaks down to Cdk and becomes inactive

What cyclins/cdks are associated with G1-S transition?

Cyclin D-Cdk4 and Cyclin E-Cdk2•

Acts during the G1-S transition

Phosphorylates Rb- This moves the cell past the restriction point (R).

What cyclins/cdks are assocoiated with the S transition

Cyclin A-Cdk2

Acts during S•

Stimulates DNA replication

What cyclins/cdks are associated with G2-M transition

Cyclin B-Cdk1

Initiates mitosis

What is the process in which cell division is stimulated (inhibition of Rb)

Cyclins D and E activate Cdk 4 and 2

in turn inactivates Rb by phosphorylating it.

When Rb becomes inactivated, the cell can progress past G1 into S phase."Inhibiting the inhibitor

What is the difference between tumor suppressor genes and oncogenes?

Tumor suppressor gene- brake pedals of the cell cycle

(Proto) Oncogenes- gas pedal of cell cycle

What are examples of tumor suppressors and (proto) oncogenes

Tumor suppressors - Rb, p21, p53(Proto)

Oncogenes - Cyclins and CDK

When UV radiation is encountered by a skin cell, a cascade of events occurs to keep the cell from dividing.

Describe this cascade

1. UV rays cause DNA Damage

2. DNA damage activates protein kinase that phosphorylates and activates p53

3. active p53 binds to regulatory region of p21 gene

4. p21 gene is transcribed/translated making tumor suppressor p21.

5. p21 inhibits cyclin and CDK resulting in cell cycle arrest (cell cannot divide)

What are the two main ways cells can die?

Necrosis and apoptosis

what is necrosis and when/how does it occur

- cell death due to injury or hypoxia (pathological)

- cell swells (inflammation) and bursts destroying neighboring cells

-process takes several days

what is the process of apoptosis? How is it stimulated

-genetically programmed cell death

-Membranes bleb, DNA cut up by caspases

- no inflammation caused, no damage to neighbor cells

- occurs in a few hours

Describe the internal apoptotic pathway

Internal signaling pathway - p53 activation -> Bax -> cytochrome c release -> activation of caspases -> breakdown of chromatin, proteins and membranes.

Describe the external apoptotic pathway

External signaling pathway - FasL binds to Fas receptor on target cell surface -> activation of caspases -> breakdown of chromatin, proteins and membranes.