Lecture 13: DNA Repair Flashcards
(134 cards)
Biological scale:
How many feet of DNA in each cell?
Humans receive how many base pairs from each parents?
Human genome is how many chromosomes?
3 feet of DNA in each cell
>3 billion base pairs from each parent
46 chromosomes
What is an absolute requirement of DNA?
High-fidelity of DNA replication is an absolute requirement. Have to replicate accurately and precisely, otherwise genome instability would occur.
DNA Damage
Occurs spontaneously or through chemical & environmental means. Normal metabolic processes in the body can also produced DNA-damaging by products.
If the damage is passed on to subsequent generations, then…
Permanent changes are left in the DNA –> mutations. If not corrected, mutations can be passed on to successive generations of cells and organisms if the mutation occurs
in the germline of multicellular organisms.
Mutations occur if
nucleotides are added incorrectly or if nucleotides base pair
incorrectly due to damage to the template DNA.
Mutations can have many effects, including
- Most will lead to no obvious phenotypes (neutral mutations)
- Some will have mild effects, such as altered pigmentation
- Some will have serious consequences
Mutations in germ (sex) cells can result in
an inherited disease
Mutations in somatic cells can result in
cancer
Mutations occur where a what residue is methylated?
Guanine residue. Methylated guanine is considered damaged.
During replication, the methylated guanine pairs with?
Thymine rather than cytosine; the other parental strand is unaffected.
When DNA polymerases synthesize new daughter strands, these mutations will become?
Fixed in the genome - half of all new daughter cells will now contain the mutation.
Sickle cell anemia mutation
Glutamic acid –> Valine
Single base change substitution causing disease
DNA polymerases actively incorporate bases that are correctly base paired through
conformational changes in the polymerase.
DNA polymerase selectively gives an error rate of about
one incorrect nucleotide in very 104 – 105 nucleotides.
tautomeric shifts
Misincorporation of bases can still occur. There is a spontaneous redistribution of protons and electrons in the bases that lead them to form isomers. These shifts are temporary.
Tautomeric shift example
Keto –> enol (for guanine and thymine)
Amino –> imino (for adenine and cytosine)
Tautomeric shifts causes which mis-matches?
C-A and T-G
In a tautomeric shift, cytosine can become what form? Matches with what?
Can become imino form and base pairs with adenine.
In tautomeric shift, guanine can become what form? Base pair with what?
Guanine can become enol form and base pair with thymine.
In tautomeric shift, adenine can become what form? Base pair with what?
Adenine can become imino form and base pair with cytosine.
In tautomeric shift, thymine can become what form and base pair with what?
Thymine can become enol form and base pair with guanine.
As the DNA polymerase (DNApol) proceeds along the template, it uses
correct base pairing to incorporate the next nucleotide in the chain.
If the template base has shifted to its rare
tautomeric form, an
incorrect base will be added since the hydrogen bonding appears correct.
The rare tautomeric form will shift back to the
common isomer, and the bases will be a mismatch.