BIOL #10: Cell Cycle & Mitosis

Question 1

Chromosome

Answer 1

Each chromosome contains a single long double helix of deoxyribonucleic acid (DNA) wrapped around proteins (e.g. histones).

Question 2

DNA

Answer 2

DNA encodes the cell’s genetic information.

The packing/coiling of the large amount of DNA in eukaryotic cells into chromosomes allows cell division to be a more manageable task
- Genetic information can move without tangling or breaking

Question 3

Chromatin

Answer 3

DNA plus the proteins that make up chromosomes are collectively called chromatin (typically when in an uncondensed state)

Question 4

Gene

Answer 4

A gene is a section of DNA that encodes a specific protein or RNA.
- Each chromosomes carries several hundred to a few thousand genes

Question 5

Chromosome Numbers

Answer 5

Every species has a characteristic number of chromosomes.
- Humans have 46.
+ 22 pairs of homologous chromosomes (called autosomes)
+ 1 pair of sex chromosomes
XX = female
XY = male

Question 6

Cell Cycle

Answer 6

The cell cycle is the life of a cell from the time it first forms from a dividing parent cell until its own division into two daughter cells.

Question 7

Interphase

Answer 7

Interphase accounts for about 90% of the cell cycle

• Cells grow large enough to divide
• Cells synthesize enough organelles to ensure the daughter cells will be normal in size and function.
• Cells copy their chromosomes in preparation for division

Question 8

Mitosis

Answer 8

Mitosis leads to the production of somatic cells, which are all cell types except gametes.

• Genetic material is copied and then divided equally.
• Daughter cells are genetically identical to the parent cell.

Important for:

• Growth/Development (and cancer)
• Wound repair
• Asexual reproduction (regeneration, budding)

Question 9

Gap Phases

Answer 9

Function of G1 and G2 phases:
- Phases in which the bulk of cell growth and organelle synthesis occurs.
- Some cells in multicellular organisms divide infrequently, if at all
+ These cells spend most of their time in G1 or a related phase called G0
* Specialized muscle and nerve cells

Question 10

S Phase

Answer 10

Function of S phase:

• Chromosome replication (DNA synthesis) occurs
• Cell growth still occurs during this phase.

Question 11

Chromosome Replication

Answer 11

Prior to mitosis, each chromosome is replicated during the S phase

• Each of the DNA copies in a replicated chromosome is called a chromatid.
• Chromatids are initially joined together along their entire length (by special proteins called cohesins) as well as at a specialized region of the chromosome called the centromere.
• The centromere contains a region of specialized proteins, called the kinetochore, where the microtubule spindle fibers attach
• The part of the chromatid on either side of the centromere is referred to as an arm of the chromatid
• Chromatids from the same chromosome are referred to as sister chromatids.

Question 12

M Phase

Answer 12

Function of M phase:

• This is the phase where cell division and cytokinesis occurs
• Usually the shortest stage in the cell cycle

Question 13

Chromosome Life

Answer 13

During the beginning of Interphase, most chromatin (DNA + proteins) is “relaxed” or uncondensed, forming long, threadlike strands.

After replication during S phase, each strand consists of two genetically identical sister chromatids attached at the centromere.

At the start of mitosis the replicated chromosomes condense.

Question 14

Prophase

Answer 14

During prophase in animal cells:

• Chromosomes condense and first become visible under the light microscope.
• The mitotic spindle forms

Question 15

Prometaphase

Answer 15

During prometaphase:
- The nuclear envelope breaks down.
- The nucleolus disappears.
- Kinetochore microtubules from each mitotic spindle attach to one of the sister chromatids of each chromosome.
+ Attachment occurs within the centromere at a specialized protein structure called the kinetochore.
- Nonkinetochore microtubules begin to push against other nonkinetochore microtubules from the opposite pole

Question 16

Metaphase

Answer 16

During metaphase, the formation of the mitotic spindle is completed.

Motor proteins on the kinetochore microtubules pull each chromosome in opposite directions, causing the chromosomes to line up in the middle of the cell.
- The imaginary plane formed by this is called the metaphase plate.

Question 17

Anaphase

Answer 17

During anaphase:
- Centromeres are split by an enzyme called separase and sister chromatids are pulled by the spindle fibers toward opposite poles of the cell.
- Replicated chromosomes split into two identical sets of unreplicated chromosomes.
+ As soon as they are no longer attached at the centromere, sister chromatids become daughter chromosomes.
- In addition, motor proteins of the polar (nonkinetochore) microtubules push the two poles of the cell away from each other (cell elongation)

Question 18

Telophase

Answer 18

During telophase:

• A new nuclear envelope begins to form around each set of chromosomes.
• The mitotic spindle disintegrates.
• The chromosomes begin to de-condense.
• When two independent nuclei have formed, mitosis is complete.

Question 19

Mitotic Spindle

Answer 19

Components of the mitotic spindle (animal cells):
- Kinetochore microtubules attach at the centromere (kinetochore) and pull chromosomes to the poles of the cell during mitosis.
- Nonkinetochore (polar) microtubules push the poles of the cell away from each other during mitosis (causes cell elongation).
- Centrosomes are the microtubule-organizing center in animal cells
+ Contain the centrioles, each composed of a cylinder of microtubules
+ In plant cells, mitotic spindles form during prophase but without centrosomes and centrioles present
- Asters are a radial array of short microtubules that extend from each centrosome to the cell membrane as anchors

Question 20

How Does The Spindle Move Chromosomes?

Answer 20

Two mechanisms are involved in the movement of sister chromatids along the kinetochore microtubules toward opposite ends of the cell

• Both these mechanisms involve motor proteins
• Both mechanisms have been observed in cells, however, the relative importance of each type during cell division depends on the cell types or species.

Question 21

Pac-Man Mechanism

Answer 21

Motor proteins on the kinetochores “walk” the chromosomes along the microtubules towards the poles by depolymerization at the kinetochores

Question 22

Reel In Mechanism

Answer 22

Chromosomes have also been shown to be “reeled in” by motor proteins at the spindle poles with microtubule depolymerization at the poles

Question 23

How Does The Cell Elongate Before Splitting?

Answer 23

Polar (nonkinetochore) microtubules from opposite poles overlap and push against each other, elongating the cell during Anaphase
- The region of overlap for the polar (nonkinetochore) microtubules is reduced as motor proteins attached to the microtubules walk them away from each other
+ This mechanism is driven by ATP
- At the same time, the polar microtubules are polymerized at the ends where they overlap so they can continue to push away from each other
+ Also requires ATP

Question 24

Cytokinesis

Answer 24

A stage in which the cytoplasm of the cell divides into two distinct daughter cells.

Typically begins by Anaphase or Telophase and completes immediately after mitosis.

Animal Cell Cytokinesis (Cleavage)

• When a ring of actin filaments and myosin motor proteins interact to contract inside the cell membrane, causing it to pinch inward in a cleavage furrow.
• This type of cytokinesis is also found in fungi and slime molds

Plant Cell Cytokinesis
- During Telophase, vesicles are transported from Golgi apparatus to the middle of the dividing cell.
+ Vesicles fuse to form a cell plate.
+ Vesicles carry material needed to build a cell wall

Question 25

Binary Fission

Answer 25

Prokaryotes reproduce by doubling their size and dividing in half – a process known as binary fission

Does not include mitosis

Bacteria do not undergo cytokinesis, but instead divide via fission, a process similar to animal cytokinesis.

Question 26

Control of Cell Cycle

Answer 26

Cell cycle length can vary greatly among cell types; variation in the length of G1 phase is responsible for these differences.

• G1 phase is essentially eliminated in rapidly dividing cells.
• Nondividing cells get permanently stuck in G1 phase; this arrested stage is called the G0 state (e.g. nerve or muscle cells)

The rate of cell division can also respond to changes in environmental conditions.

Variations in cell cycle length suggest that the cell cycle is regulated and that regulation varies among cells and organisms.

Cell Cycle control system

• Experimental evidence suggest that the cell cycle is driven by specific signaling molecules present in the cytoplasm
• This control system involves a cyclically operating set of molecules that both trigger and coordinate key events in the cell cycle
• Includes checkpoints regulated by both internal and external signals

Question 27

Mitosis-Promoting Factor

Answer 27

Mitosis-promoting factor (MPF) is present in the cytoplasm of M phase cells and induces mitosis in all eukaryotes.

MPF is composed of two distinct subunits: a protein kinase and a cyclin.

• The protein kinase is an enzyme that catalyzes the transfer of a phosphate group from ATP to a target protein (phosphorylation).
• The cyclin subunit functions as a regulatory protein.

Question 28

Cyclin-Dependent Kinase

Answer 28

The MPF protein kinase is a cyclin-dependent kinase (Cdk) that is active only when bound to the cyclin subunit. Thus, when cyclin concentrations are high, more MPF is active and more target proteins are phosphorylated, initiating mitosis.

The concentration of MPF cyclin increases during interphase, then peaks in M phase before decreasing again.

Question 29

MPF Activation

Answer 29

After it binds to cyclin, MPF’s Cdk subunit becomes phosphorylated at two sites, rendering it inactive.

Late in G2 phase enzymes cause one of the phosphate groups on the Cdk subunit to drop off.
- This dephosphorylation reaction changes MPF’s shape, activating it.

Once MPF is activated, it triggers a chain of events, culminating in the condensation of chromosomes and formation of the mitotic spindle apparatus.

Question 30

MPF Deactivation

Answer 30

During Anaphase, an enzyme complex begins degrading MPF’s cyclin subunit. In this way, MPF triggers a chain of events that leads to its own destruction.

The Cdk persists in the cell, inactive, until new cyclin molecules are made during the S and G2 phases of the next cell cycle

Question 31

Cell-Cycle Checkpoints

Answer 31

A checkpoint in the cell cycle is a control point where ‘stop’ and ‘go ahead’ signals can be regulated
- Such signals involve signal transduction pathways

There are three distinct cell-cycle checkpoints during the four phases of the cell cycle (G1, G2 and Metaphase checkpoints)

Interactions among regulatory molecules at each checkpoint allow a cell to “decide” whether to proceed with division. If these regulatory molecules are defective, the checkpoint may fail and cells may start dividing in an uncontrolled fashion.

The three cell-cycle checkpoints prevent the division of cells that are damaged or that have other problems, and they prevent the growth of mature cells that should stay in the G0 state.

Question 32

G1 Checkpoint

Answer 32

The first and most important checkpoint occurs late in G1. This checkpoint determines whether the cell will continue through the cycle and divide, or exit the cycle and enter G0.

Four factors affect whether cells pass the G1 checkpoint:

1) Cell size
2) Nutrient availability
3) Social signals from other cells
4) Health of DNA

Question 33

Will a Given Cell Pass the G1 Checkpoint?

Answer 33

Cells must be large enough to split into two functional daughter cells.

Food must be sufficient for cell growth.

Cells in multicellular organisms pass (or do not pass) through the G1 checkpoint in response to signaling molecules from other cells.

• Certain cells release proteins called growth factors that stimulate other cells to divide
• High density can inhibit division via growth-inhibiting signals between adjacent cells

Question 34

p53

Answer 34

The p53 protein either pauses the cell cycle or initiates apoptosis – programmed cell death – if the DNA is physically damaged.
- p53 is an example of a tumor suppressor (checkpoint regulatory molecule) – damage to the p53 gene can lead to uncontrolled cell division.

Question 35

G2 Checkpoint

Answer 35

The second checkpoint is after chromosome replication, between the G2 and M phases.

Cells stop growing at this check point if chromosome replication has not proceeded properly or if DNA is damaged.

Activated MPF must be present for mitosis to begin (i.e. high level of cyclin)

Question 36

Metaphase Checkpoint

Answer 36

The third and final checkpoint is during the M phase.

• Cell division ceases during metaphase if the chromosomes are not properly attached to the mitotic spindle.
• This mechanism prevents incorrect chromosome separation that could give daughter cells the wrong number of chromosomes.

Question 37

Cancer

Answer 37

Cancer is a common, sometimes lethal disease that affects many humans.

Cancer is a complex family of diseases caused by cells that grow in an uncontrolled fashion, that invade nearby tissues, and that spread to other sites in the body.

Cancers vary widely in time of onset, growth rate, seriousness, and cause.

Despite their differences, all cancers arise from cells in which cell-cycle checkpoints have failed (e.g. p53).
- Cancers are thought to arise from cells with defects in the G1 checkpoint.

Question 38

Types of Cancerous Cell Defects

Answer 38

Cancerous cells have two types of defects:

1) Defects that make the proteins required for cell growth active when they should not be
2) Defects that prevent tumor suppressor genes (e.g. p53) from shutting down the cell cycle

Most cancers result from multiple defects in cell-cycle regulation.

• Most cancers develop only after several genes have been damaged.
• This combined damage is enough to break cell-cycle control and induce uncontrolled growth and metastasis.

Each type of cancer is caused by a unique combination of errors.

Question 39

Tumor

Answer 39

A tumor forms when one or more cells in a multicellular organism begin to divide in an uncontrolled fashion.

Question 40

Metastasis

Answer 40

When cancer cells detach from the original tumor and invade other tissues, this is called metastasis.

Question 41

Benign Tumors

Answer 41

Benign tumors are noninvasive and noncancerous.

- Do not transform adjacent tissues and do not spread

Question 42

Malignant Tumors

Answer 42

Malignant tumors are invasive. They can spread throughout the body via the blood or lymph, and initiate secondary tumors.

Question 43

Social Control

Answer 43

Cells respond to signals from other cells, so that cells divide only when their growth benefits the whole organism. This is known as social control.

Social control is based on growth factors–polypeptides or small proteins released by cells that stimulate division in other cells (paracrine signaling).
- Generally, cell cultures will not grow unless growth factors are present.

Cancer cells, however, divide without growth factors. They are no longer subject to social control at the G1 checkpoint.