Chapter 10: 10.1 Repair and Recombination Flashcards
Mutations in DNA occur when…
There is a change in the normal DNA sequence
What are spontaneous mutations known as?
Point mutations
What can point mutations be caused by?
- Errors in DNA replication
- Environmental exposure to damaging agents (UV light, radiation etc.)
- Harmful chemicals/toxins
- Byproducts of normal cell metabolism (e.g. lipid oxidation)
What are the types of point mutations?
- Nonsense mutations
- Missense mutations
- Silent mutations
Nonsense mutations
A premature stop codon is introduced into a sequence
Missense mutation
A change to the amino acid sequence
Silent mutation
No change to the amino acid sequence
Can mutations be beneficial?
Mutations can be:
* Beneficial
* Benign
* Harmful
Beneficial mutations
Improves the fitness of an organism
Examples
* Resistance to a virus
* Lactose tolerance
Benign mutations
Does not change the overall fitness of an organism
Examples
* Change in eye color or silent mutations
Harmful mutations
Negatively impacts the fitness of an organism
Examples
* Development of diseases (cancer, birth defects)
DNA polymerases make a mistake approximately every…
1 in 10,000 bases
What is the actual number of mistakes that researchers found in DNA?
1 in 1,000,000,000 bases
Processes:
DNA Replication Proofreading
- The DNA polymerase(s) pause
- 3’-5’ exonuclease removes the incorrect base pair
- DNA polymerase(s) adds the correct one
What is Base Excision Repair used to repair?
- Spontaneous natural deamination (C becomes U, resulting in a G-U mismatch)
- Depurination (loss of A or G) lesions
Processes:
Base Excision Repair (BER)
- DNA glycosylase identifies + removes U from sugar-phosphate backbone
- APE1 endonuclease removes deoxyribose phosphate that is abasic
- Specialized DNA polymerase adds a C
How does DNA glycosylase remove the base?
Flips the base out of the helix and removes it
When are Base Excision Repairs done?
BEFORE replication to prevent the mutation becoming permanent
What does Mismatch Excision Repair do?
Fixes mutations that include:
* Base pair mismatches
* Small insertions/deletions of a few nucleotides
When does Mismatch Excision Repair occur?
Made AFTER replication
What is thought to be the mechanism behind Mismatch Excision Repair?
- Specialized proteins determine which strand is the template and which is the mutated daughter strand
- An endonuclease removes the mismatch/insertion/deletion
- The daughter strand is repaired to produce an exact copy of the template strand
What does Nucleotide Excision Repair fix?
A mutation that causes a distortion in the double helix structure of DNA
* E.x. Thymine dimers
What is the process of Nucleotide Excision Repair?
- Distortion is identified by a complex of XP-C and 23B proteins
- TFIIH helicase, RPA, and XP-Gunwinds the DNA at this site
- XP-G and XP-F work as endonucleases to cut out the distorted segment of DNA
- DNA polymerase fills in the gap
What are the two main systems for repairing double stranded DNA breaks?
- Non-homolgous end joining
- Homologous recombination
How does NHEJ work?
Joins 2 non-homologous ends of DNA together
* The two strands are usually still close enough together that they will be ligated back together
What are some issues with NHEJ?
- Causes minor deletions
- N-terminus of one gene can fuse to the C-terminus of a different gene
True or False:
Small deletions from either ends in NHEJ is a major issue
Not necessarily
* Majority of DNA is noncoding/intronic DNA
Why is the fusing of the N-terminus of one end and the C-terminus of the other end problematic?
Results in chimeric genes
* Can result in changes to cell function
* Can result in cancer
How does Homologous Recombination?
Damaged DNA sequence is copied from an undamaged or highly similar (homologous) copy of DNA
* Repaired by an exchange of two different DNA strands (recombination)
True or False:
Homologous Recombination is error-free
True
