PL2 Flashcards
What is DNA subject to
Constant damage
What are mutations
Permanent, transmissible changes to the genetic material of a cell
When can mutations occur
Spontaneously, by transposable events and by errors during replication
Do mutations transmit to baby in osmotic cells
No
What are mutagens
Chemical compounds, uv radiation or ionizing radiation that increase the frequency of mutations
What does accumulating damage in somatic cells cause
Causes them to lose control over their growth and become cancerous
What are carcinogens and what can they be described as
Agents that cause cancer, are often mutagens
What can carcinogens cause
Self-sufficiency in growth signals
Insensitivity to antigrowth signals
Evasion of apoptosis
Limitless replicative potential
Tissue invasion and metastasis
Sustained angiogenesis
What are examples of DNA repair
Proofreading by DNA polymerase
Base excision repair
Mismatch excision repair
Nucleotide excision repair
Double strand break repair by end joining or by homologous recombination
What kind of activity do polymerases have and what does it affect
Proofreading activity that helps increase accuracy
Which polymerases have proofreading or a 3’ to 5’ exonuclease
Polymerase epsilon and fancy s but not alpha
What happens with the incorporation of an incorrect base
causes polymerase to pause and the 3’ end of the new strand is free to move to the 3’ to 5’ exonuclease site and the mispaired base is removed
What does an exonuclease do
Digests nuclear at one end and takes incorrect nucleotide away
What is the most common point mutation
C to T
What are the steps that cause mutation in DNA by a single base pair
Spontaneous Deamination (c turns to T)
Replication (causes permanent mutation in DNA) that makes two double stranded DNA from a single double stranded DNA
What are the two double stranded DNAs made from replication if mutation isn’t caught
Mutant DNA and wild type DNA
Where must repair occur in and what happens once there is repair in base excision repair
After deamination but before replication otherwise there will be a permanent mutation in DNA
In a mismatched base pair, which base is correct and which one is wrong
T-G mismatches almost always result from deamination of C to U or C to T so T is wrong and should be replaced by C
What are the overall steps of base excision repair (BER)
- DNA glycosylase breaks the bond between T and the sugar phosphate backbone
- APEI endonuclease cuts the DNA strand where it is missing a base
- AP lease removes deoxyribose in phosphate leaving a one nucleotide gap
- Special DNA polymerase (B) inserts C using G as template, ligand repairs sugar-phosphate backbone
What does mismatch excision repair do
Fixes errors introduced during replication, including base pair mismatches and insertions or deletions of one or a few nucleotides
In mismatch excision repair, which strand is wrong?
The newly synthesized strand is wrong
When does mismatch excision repair happen
After DNA replication
How is the newly synthesized strand distinguished in mismatch excision repair
3’ end of newly synthesized strand is distinguishable from old strand
How does mismatch excision repair work
MSH2 and MSH6 recognize the mismatch and distinguished newly synthesized strand
This triggers binding activity of MLH1 endonuclease that cuts newly synthesized strand
DNA helices unwinds and DNA exonuclease digests several nucleotides of daughter strand
DNA polymerase (fancy S) fills in the missing nucleotides using the other strand as template and ligand repairs the sugar-phosphate backbone
