Cell sTRESS

Question 1

threats to the cell

Answer 1

Damage to proteins, lipids, nucleic acids  chemical or physical insults 

Nutrient deprivation 

loss of metabolic energy supply and/or building blocks for macromolecules

 Toxins (various actions)  (Infections)  may cause nutrient deprivation or other chemical changes (bacteria), or  Invade cells (viruses), or  produce biological toxins (bacteria)

Question 2

DNA damage has unique consequences /Rna

Answer 2

Single copy of encoded information

 Mutation  permanent, may be lethal to the cell, or to the organism 

Lasting damage from a single chemical change 

Damage must be repaired, or else!

RNA
Multiple copies in cell 

Damaged components may malfunction 

Or they may interfere with normal function of remaining intact molecules

 Damage more diffuse

 Need to replace damaged components with new ones

Question 3

What type of DNA damage is repaired by BER?

Answer 3

BER is used by the cell to correct damaged DNA bases or single-strand DNA breaks. These lesions often result from spontaneous DNA damage (DNA deamination or hydroxylation of bases) or by exposure to environmental alkylating agents.

Question 4

What does the Loss or change of DNA bases occur by ?

Answer 4

Loss or change of DNA bases by spontaneous chemical reactions

Question 5

Thymine

Answer 5

Thymine dimers induced by UV light

5-methyluracil, thymine (T) is a pyrimidine nucleobase, which pairs with adenine (A), a purine nucleobase. They are joined together as a base pair by two hydrogen bonds, which stabilize the nucleic acid structures in DNA.

Question 6

What do Enzymes do ?

Answer 6

Enzymes recognise chemically altered single DNA bases and replace them

Question 7

Repaired by Excision of a segment of DNA

Answer 7

More extensive damage (e.g., UV-induced dimers) get repaired by excision of a DNA segment

Question 8

Why are Double Strands are harder to break ?and important to repair ?

Answer 8

No template strand available to identify correct sequence 

May disrupt DNA replication

 May disrupt proteins even if a strand breaks in an intron

 Two strategies:  Non-homologous end joining  Homologous recombination

Question 9

During DNA replication, the newly made strand guides repair of a strand break by “homologous recombination”

Answer 9

Homologous Recombination

Question 10

What occurs during DNA replication

Answer 10

During DNA replication, the newly made strand guides repair of a strand break by “homologous recombination

Question 11

What occurs during Mitosis ?

Answer 11

During mitosis, the sister chromatid may provide information for accurate repair by homologous recombination

Question 12

DNA damage is sensed before, during, and after DNA synthesis

Answer 12

DNA damage detected here G2/M point

Starting Point

Question 13

Cells audit themselves for DNA damage

Answer 13

A cell 4 hours after ionising radiation. Red/green pairs show multiprotein complexes assembled at sites of DNA damage.

Question 14

Cellular outcomes of DNA damage

Answer 14

In response to DNA damage cells might:

• Repair the DNA
• Stop in cell cycle to repair DNA
• Go in permament cell cycle arrest (senescence) -

Activate apoptosis

Question 15

What do P53 activate ?

Answer 15

P53 activates DNA damage……

Question 16

via activation of expression of p21 and XPC

Answer 16

P53 can cause DNA repair - via transcriptional induction of p21. P21 binds PCNA (proliferating cell nuclear antigen), a protein that has a role in DNA synthesis and repair. - Via transcriptional activation of XPC, a protein involved in nucleotide excision repair

Question 17

Summary: DNA damage

Answer 17

Examples 

Loss of bases (e.g., depurination)

 Change of single bases (e.g., deamination)  Dimerisation(UV-induced) 

Strand breaks

 Replication errors by DNA polymerase

Normal rate of damage too high for survival

 Repair mechanisms required

Question 18

Where does Protein Folding occur ?

Answer 18

Protein folding begins during translation at the ribosome

Protein folding is disrupted at elevated temperature

Question 19

Is proteins Folded ?

Answer 19

In cells, protein folding is assisted and monitored

Misfolded and aggregated proteins may accumulate in cells subjected to heat stress (for example

) • Deprives cell of the affected protein functions, and aggregates may be toxic

Question 20

“Molecular chaperones”

Answer 20

perform the same function for proteins.

prevent both newly synthesised polypeptide chains and assembled subunits from aggregating into nonfunctional structures.

Question 21

What do the HEAT SHock Protein ?

Answer 21

“Heat shock protein”-70 binds hydrophobic regions of unfolded proteins to prevent aggregation

Question 22

What occurs during the HP60 LATER ?

Answer 22

Later during folding, Hsp60 provides a protected environment for protein folding

Question 23

What does the Proteasome ?

Answer 23

The “proteasome” degrades misfolded and ubiquitin-tagged proteins

Question 24

Complex Sugars are attached to what ?

Answer 24

In the ER, complex sugars are attached to growing polypeptides

Question 25

Er Glycoproteins ?

Answer 25

ER glycoproteins are monitored for folding by the combined action of a glucosyl transferase and calnexin

Question 26

Where Aare the Badly ones sent to ?

Answer 26

Badly misfolded ER proteins are sent back to the cytosol and degraded by the proteasome

Question 27

Where does the increased Temperature do ?

Answer 27

Increased temperature raises the level of unfolded proteins, directing the production of more chaperones

Question 28

Heat shock Response is what ?

Answer 28

The heat shock response is an example of negative feedback regulation, which allows cells to adapt to stress

Question 29

protein folding stress

Answer 29

Protein misfolding occurs all the time

 Controlled by chaperones (Hsp70, Hsp60) and the proteasome

 Worsened by elevated temperature and other factors, such as:  High level of secretory protein production  Viral infection (making viral coat proteins) 
When occupied by unfolded proteins,

Hsps are released from stress-responsive transcription factors

 The transcription factors go to the nucleus and direct the production of more heat shock proteins 

This increases capacity to cope with misfolding