Module 11 Flashcards

(39 cards)

1
Q

Cell Division

A

How can a cell make more cells?
Use a process known as → cell division
Why does cell division occur?
For several reasons including
Cell growth
Cell replacement
Cell healing
Cell reproduction

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2
Q

Cell Division must satisfy important requirements

A

i. After cell division, the 2 daughter cells that result must each receive all of the genetic material found in the single parent cell
ii. The parent cell needs to be big enough to divide in 2, so each daughter cell receives adequate cytoplasmic components
Prokaryotic cells divide by → binary fission
Eukaryotic cells divide by → mitosis & cytokinesis

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3
Q

Binary Fission

A

Process of cell division in prokaryotes
DNA Replication → circular DNA molecule
Increase in cell size
Division into 2 daughter cells → each daughter cell receives one copy of the replicated parental DNA

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4
Q

Steps of binary fission

A

Steps of Binary Fission
Proteins bind the circular genome to the inner surface of the plasma membrane
DNA replication starts at a certain spot on the molecule and travels around the circle in opposite directions
2 DNA molecules are produced → both of which are affixed to the cell membrane
The 2 DNA attachment sites separate as the cell elongates during binary fission
A constriction forms at the midpoint of the cell when it is about twice its original size & the DNA molecules are well-separated
At the location of the constriction
A new membrane is created
A new cell wall is created
This produces 2 daughter cells that are identical to the parent cell

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5
Q

Eukaryotic Division

A

Reproduce by mitotic cell division
Genome in Eukaryotes → large & linear
b/c it is in the cell nucleus of a eukaryote → the genetic material is isolated from the other components of the cell

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6
Q

Comparison of Cell Division

A

Process of DNA replication in both eukaryotes & prokaryotes is similar
But there are some important differences in cell division when comparing these cells

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7
Q

DNA Replication

A

In eukaryotes, cell division occurs through a series of stages known as the → cell cycle
The cell cycle consists of 2 distinct stages
The time during which the parent cell divides into 2 daughter cells → M phase
The time between 2 successive M phases → interphase

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8
Q

M Phase

A

When the parent cell divides into 2 daughter cells and consists of
Separation of replicated chromosomes → mitosis
Division of the cytoplasm into 2 daughter cells → cytokinesis

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9
Q

Interphase

A

Occurs between 2 successive M phases
Lasts about 10-14 hours
Cell makes many preparations for division including
DNA replication in the nucleus
Increase the size of the cell
Interphase is broken down into 4 stages

  1. G1 → increase in cell size and protein content
    First “gap” phase
    Preparing the cell for S phase
    Synthesis and activation of regulatory proteins
  2. S → The “synthesis” phase → replication of the DNA
  3. G2 → the second “gap” phase
    Cell prepares for M phase
  4. Go
    - Separate from G1 Phase → no active preparation for cell division
    Occurs in cells that do not actively divide → e.g., liver cells
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10
Q

DNA Replication

A

Semiconservative
2 Strands of Parental DNA unwind → each strand serves as a template strand for the synthesis of a daughter strand

At the end of DNA replication each new DNA molecule consists of
One strand → old parental
One strand → newly synthesized
Semi-conservative

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11
Q

DNA Replication Process

A

There are many enzymes needed to replicate DNA:

Helicase
Unwinds the parental double helix at the replication fork
Allows a single strand of DNA to be available for complementary base-pairs to be added by DNA polymerase

Single-strand binding protein
Binds to the single-stranded regions of the parental strands
Prevents the parental strands from coming back together

Topoisomerases
Works upstream of the replication fork
Changes the supercoiled state of DNA → caused by the unwinding of the double helix at the replication fork

DNA polymerase
Adds to the nucleotide strand
Requires 4 deoxyribonucleotides → dATP, dCTP, dGTP, dTIP
Requires a DNA template & RNA primer strand with a 3’-OH terminus
Can only synthesize DNA in a 5’ to 3’ direction → same as for transcription
Most DNA polymerases can correct mistakes that may happen during replication

RNA primase (many enzymes needed to replicate DNA)
Synthesizes a short piece of RNA that is complementary to a sequence of the DNA parental strand
Is needed so the DNA polymerase can add DNA bases to the growing chain

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12
Q

Leading & Lagging Strands

A

Since newly synthesized DNA can be elongated only at the 3’ end, the 2 daughter strands use different replication mechanisms
One strand grows toward the replication fork & synthesized continuously → leading strand
One strand grows away from the replication strand & synthesized discontinuously as fragments → lagging strand

Leading Strand:
Has its 3’ end point toward the replication fork
Synthesized as one long, continuous polymer as the parental strand is unwound
Lagging Strand
Has its 3’ end point away from the replication fork
Synthesized in short, discontinuous pieces called → okazaki fragments
A new short piece of the lagging strand is initiated at intervals as the parental DNA strand is unwound at the replication fork

Need to:
Add an RNA primer
Then, have DNA polymerase extend the RNA primer
Then, replace RNA primer w/ DNA bases
Okazaki Fragments are a necessity of DNA replication due to synthesis in one direction → 5’ to 3’ direction

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13
Q

RNA Primers

A

Short RNA Primers are added by an RNA polymerase → RNA primase
Synthesizes a short piece of RNA complementary to the DNA
Once the primer has been synthesized → DNA polymerase takes over and elongates the primer adding DNA nucleotides
Until it hits the fragment in front of it
A different DNA polymerase removes the primer and replaces it with DNA

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14
Q

DNA Ligase

A

When the replacement of the RNA primer with new DNA is complete, the fragments are joined together with an enzyme → DNA ligase
Completes the sugar-phosphate backbone of the new DNA

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15
Q

Synthesizing Leading & Lagging Strands

A

The strands are synthesized at the same time
This is accomplished by looping of one of the strands of the DNA → trombone model

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16
Q

Proofreading

A

Most DNA polymerases can correct their own errors through → proofreading
Hydrogen bonds temporarily hold the new nucleotide and the base across the way in the template strand → an opportunity to check for errors
DNA polymerase can correct errors because it detects the mispairing in hydrogen bond formation
DNA polymerase activates a cleavage function
Removes the incorrect nucleotide
Then inserts the correct one in its place

17
Q

Prokaryotic Replication

A

Background
Replication of circular DNA
Happens in most bacteria
Both mitochondrial and chloroplast DNA also replicate in this way since they are circular

18
Q

Circular Chromosome Replication

A

2 Special Features of replication of circular chromosomes
There is a single origin of replication
Replication proceeds in both directions until the replication forks meet and fuse on the opposite side → this completes one round of replication

19
Q

Eukaryotic Replication

A

Background
Eukaryotes have linear DNA
There are multiple origins of replication → results in multiple replication forks
Each replication fork → proceeds bidirectionally
Each replication fork has a leading and lagging strand
When 2 replication bubbles meet → DNA ligase seals the gap in the sugar-phosphate backbone

20
Q

Replicating End of Linear DNA

A

The leading DNA strand can be replicated all the way to the end of the template DNA strand
But because the DNA is linear it leads to a problem at the end of replication
The lagging DNA strand needs enough single-stranded template DNA to begin the next okazaki fragment
The final primer is added about 100 nucleotides form the 3’ end of the template
When the primer is removed → a section of template DNA remains unreplicated
Each time the DNA is replicated one strand is shortened
Eventually the DNA would severely shorten after several cycles

21
Q

Eukaryotic Telomeres

A

Ends of the linear chromosomes are called → telomeres
The repeated sequence and the # of repeats varies between species
In humans the sequence → 5’-TTAGGG-3’ is repeated 1500-3000 times at each telomere
In some cell types the missing nucleotides are replaced with the enzyme → telomerase
The enzyme telomerase can extend the ends of the chromosome to address the chromosome shortening

22
Q

Telomerase

A

Telomerase activity is cell-type specific → not every cell has telomerase activity

It is fully active in:
i. Stem cells
ii. Germ cells (sex cells) → produce eggs or sperm

It is inactive in adult somatic cells
Mitotic division can occur only about 50 times before the telomeres become so short that the cells stop dividing → Hayflick limit

Telomerase:
Is a ribonucleoprotein → protein-RNA complex
Carries its own primer → template RNA
Has reverse transcriptase activity
RNA → DNA

Adds nucleotides to 3’-OH end of lagging strand template to prevent shortening → it polymerizes deoxyribonucleotides directed by RNA template
This RNA template is part of the enzyme
It is complementary to the telomeric repeats
Results in an extra 3’ overhang which can form loops at the end of chromosomes
Protection from degradation

23
Q

Eukaryotic DNA Packaging

A

Background
In eukaryotic cells, DNA is organized with histones and other proteins into chromatin
The chromatin can be looped and packaged to form chromosomes
*Chromosomes become visible only in cells about to divide
A cell with one copy of each chromosome is → haploid
A cell with 2 copies of each chromosome is → diploid
For cell division to proceed, every chromosome in the parent cell must be duplicated so that each daughter cell receives a full set of chromosomes
This duplication takes place during S phase
After DNA replication there are 2 identical copies called → sister chromatids
Even though the DNA in each chromosome is duplicated they do not separate
They stay side by side, held together at the centromere
Hard to see the chromosomes during interphase → not condensed

24
Q

Mitosis

A

Stages of Mitosis
The chromosomes become condensed as the cell moves from G2 to the start of mitosis
Each of the 5 stages of mitosis can be determined using a microscope depending on the position of the chromosomes
Remember, mitosis = karyokinesis = nuclear division

25
Mitosis: Stage 1 - Prophase
Characterized by the appearance of visible chromosomes Outside of the nucleus the cell assembles a structure known as the → mitoic spindle Made of microtubules that pull the chromosomes apart into separate daughter cells The microtubule-organizing centers for animal cells → centrosomes Are duplicated and begin to migrate to opposite poles Plant cells also have microtubule-based mitotic spindles → but they lack centrosomes
26
Mitosis: Stage 2 - Prometaphase
The nuclear membrane breaks down and the microtubules of the mitotic spindle attach to the chromosomes The microtubules grow and shrink to explore the region that was once the nucleus As the ends of the microtubules encounter chromosomes → they attach to the centromeres of the chromosomes Each centromere is associated with 2 protein complexes called → kinetochores One kinetochore on each side of the centromere Each kinetochore is associated with one of the two sister chromatids Site of attachment for a single microtubule This arrangement is key for the separation of sister chromatids later in mitosis
27
Mitosis: Stage 3 - Metaphase
One of the most visually distinctive stages of the cell during mitosis The spindle microtubules lengthen and shorten This pushes the chromosomes toward the center of the cell → aligns at the metaphase plate This is a single plane that is roughly equidistant from both spindle poles
28
Mitosis: Stage 4 - Anaphase
The centromere divides and kinetochore microtubules shorten This pulls the chromatids apart toward the centrosome → ensures that one chromatid from each pair go to opposite poles
29
Mitosis: Stage 5 - Telophase
Complete set of chromosomes arrives at a spindle pole and cytosolic changes occur in preparation for the cell’s division The microtubules of the mitotic spindle break down and disappear The nuclear envelopes begin to re-form around each set of chromosomes → creates two nuclei Once the nuclear envelope is re-formed the chromosomes decondense and are less visible Telophase marks the end of mitosis
30
Cytokinesis: Cytokinesis - Animal Cells
The next step in M phase is the division of the parent cell into 2 daughter cells → cytokinesis Cytokinesis begins with a ring of actin filaments that forms on the inner face of the cell membrane called the → contractile ring Forms at the equator of the cell perpendicular to the axis of what was the spindle The ring contracts → pinches the cytoplasm of the cell Divides it into 2 daughter cells
31
Cytokinesis: Cytokinesis - Plant Cells
Mitosis is for the most part similar in animal and plant cells → but cytokinesis is different This is b/c plant cells have a cell wall and will need to construct a new cell wall for division to occur The plant cells form a structure called the phragmoplast in the middle of the cell during telophase The phragmoplast consists of overlapping microtubules These guide vesicles containing cell wall components to the middle of the cell Then during late anaphase and telophase the vesicles fuse to form a new cell wall in the middle of the dividing cell called the → cell plate The cell plate will fuse with the original cell wall at the perimeter of the cell This completes cytokinesis
32
Progression
Introduction It is important to control the cell cycle There are 2 events that are critical Initiation of DNA replication → G1 / S transition Initiation of mitosis → G2 / M transition Cells must have regulatory mechanisms to progress through the cycle Without these mechanisms the cell may undergo cell death or divide uncontrollably → cancer development
33
Cyclins & CDKs
Through the cell cycle there is cyclic activity of protein and kinases → their combined activity controls cell cycle progression What are these proteins & kinases? Cyclins → regulatory protein subunits of specific protein kinases Their levels rise and fall with each turn of the cell cycle CDKs → kinases that phosphorylate other proteins whose actions are necessary for the cell cycle to progress Always present in the cell Active only when bound to appropriate cyclin
34
Cyclin-CDK Complexes
There are several different cyclins and CDK Act at specific steps of the cell cycle During G1 phase → the levels of cyclin D & E rise and activate CDKs It prepares the cell for S phase For example, it activates transcription factors that lead to the expression of DNA polymerase During S phase → cyclin-A levels increase, activating CDKs that initiate DNA synthesis During G2 phase → levels of cyclin B rise activating CDKs that initiate multiple events associated with mitosis Breakdown of nuclear envelope in prometaphase Formation of the mitotic spindle
35
Cell Cycle Checkpoints
At various stages of the cell cycle, checkpoints make sure the cell is ready to move on to the next phase There are 3 major stages in the cell cycle i. DNA damage checkpoint Checks for damaged DNA b4 it enters S phase ii. DNA replication checkpoint Checks for the presence of unreplicated DNA at the end of G2 b4 the cell enters mitosis iii. spindle assembly checkpoint Checks that all of the chromosomes are attached to the spindle before the cell progresses with mitosis
36
DNA Damage Checkpoint
If DNA is damaged by radiation → activates a protein kinase that phosphorylates the p53 protein When p53 is phosphorylated, its level in the nucleus rises → this activates the transcription of several genes One of which is an inhibitor that blocks the activity of the G1/S cyclin-CDK complex → arrests the cell at the G1/S transition Gives the cell time to repair the DNA damage P53 is often called → guardian of the genome
37
DNA Not Repaired
What happens if the damage is not repaired in time? Once p53 is activated the DNA needs to be repaired quickly because phosphorylated p53 also.. Stimulates transcription of the Bax gene which codes for → Bax protein Represses transcription of the Bcl-2 gene which codes for → Bcl-2 protein In a healthy cell there is a balance of Bax & Bcl-2 → make Bax/Bcl-2 dimers This will shift the overall concentrations of Bax & Bcl-2 which results in the formation of → Bax / bax dimers
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Apoptosis
The increase of Bax/Bax dimers activates the pathway for programmed cell death → apoptosis This results in a controlled and orderly disintegration of the cell Apoptosis is important in the developing embryo → allows for remodeling of tissues E.g., developing hand looks like a paddle until cells are selectively killed In the adult → apoptosis has several important functions Maintenance of tissue size → eliminate excess cells to balance cell proliferation Elimination of specific cells → e.g., removal of activated T lymphocytes that are no longer required Elimination of genetically damaged cells → cells that are irreparable need to be removed The loss of the ability of cells to undergo apoptosis is a step to becoming cancerous
39
Cancer
Group of diseases characterized by uncontrolled cell division There are cancer-causing genes known as → oncogenes First discovered in viruses Also altered version of proto-oncogenes → normal genes important in cell division Have the potential to become mutated into oncogenes There are tumour suppressor genes → inhibit cell division P53 protein is an example of a tumour suppressor The key is that cell division is regulated by Proto-oncogenes that promote cell division And tumour suppression genes that inhibit cell division This is a counterbalance system → must agree for cell division to take place Key features of cancer cells Ability to divide on their own without growth signals Resistance to inhibitory or cell death signals Ability to invade tissues → metastasis Promote new blood vessel formation → angiogenesis