L14-Maintenance of genomic integrity

Question 1

What are the three main ways that damage to DNA can occur?

Answer 1

• Copying errors during DNA repair
• spontaneous depurination (chemical damage)
• Exposure to different agents e.g. UV light

Question 2

What are the 5 major types of DNA repair?

Answer 2

• Direct reversal of the damage
• Base excision repair - corrects DNA damage caused by reactive oxygen species etc.
• Nucleotide excision repair-Removes sections of damaged DNA
• Homologous recombination repair -repairs DNA double strand breaks
• DNA mismatch repair - repairs copying errors made during replication

Question 3

What are the two major forms of UV induced DNA lesions?

Answer 3

Tymine dimers - adjacent thymines are covalently linked

6-4 photoproducts - covalent binding of thymine and cytosine

Question 4

What is ligation?

Answer 4

the joining of two DNA strands or other molecules by a phosphate ester linkage

Question 5

What is enzymatic revesal give an example?

Answer 5

Enzymatic reversal is the use of enzymes to correct the damage of the DNA. This can be done in terms of UV induced dimers by the enzyme photolyase and light to monomerise the dimers.

Question 6

How does base excision repair work?

Answer 6

Glycoslyase enzyme is used to remove the damaged base and then other enzymes are used to add new nucleotides onto the DNA. They are ligated together.

Question 7

What deoes nucleotide excision repair work on and repair?

Answer 7

It works only on double stranded DNA so cannot work on DNA during synthesis when it is single stranded. Works by removing large parts of damaged DNA such as thymine dimers and then repairs the gap.

Question 8

What is daughter strand gap repair?

Answer 8

When DNA is replicated and found to have dimers, gaps are left in the daughter DNA opposite the dimers. This means that once the double stranded DNA has formed then the simers can be removed by nucleotide excision repair.

Question 9

What is xeroderma pigmentosum?

Answer 9

It is an autosomal recessive condition in which cells have a defect in their nucleotide excision repair resulting in increased sensitivity to UV light. This increases risks of cancers.

Question 10

What is the mechanism of nucleotide excision repair?

Answer 10

The XPC protein (exeroderma pigmentosum group C) identifies problems with DNA damage. This then recruits XPB and XPD which surround the lesion and begin to unwind the DNA. XPF and XPG nucleases then cleave the DNA. DNa polymerases then repair the missing segment.

Question 11

What are the main genes involved in double strand break repair?

Answer 11

BRCA1 and BRCA2

Question 12

What are the two main ways that double strand breaks are repaired?

Answer 12

Non-homologous end joining

Homologous recombination repair

Question 13

What is the mechanism for homologous recombination repair?

Answer 13

Rad51 is key to this process. It forms nucleoprotein filament to stabalise breaks and recruits repairing proteins. Its activity is regulated by BRCA2.

Question 14

What is the mechanism for non-homologous end joining?

Answer 14

It is RAD51 independent and does not require BRCA2. Involves non homologous ends joinging and being processed so gap filling and ligation can occur.

Question 15

What does DNA mismatch repair do?

Answer 15

Repairs copy errors made during DNA replication.

Question 16

What cancer does mutation in DNA mismatch repair most commonly cause?

Answer 16

Hereditary non polyposis colorectal cancer. This is because it leads to microsatellite instability.