DNA Repair

Question 1

Mismatch Repair (MMR)

Answer 1

repaires polymerase replication errors (incorporation of incorrect base) EXCEPT accidental incorporation of uracil or base analogs
an enzyme recognizes the mismatch (recognizes old strand by methylation)
an endonuclease cuts nick in one side of phosphodiester backbone on new strand
an exonuclease removes surrounding DNA
DNA polymerase synthesizes the region
ligase seals the nick

Question 2

Base Excision Repair (BER)

Answer 2

repairs abnormal bases in DNA that arise due to base hydrolysis (deamination of cytosine to uracil or thymine, depurination of guanine)
or incorporation of base analogs or uracil by DNA pol
glycosylase scan minor groove and excise the base leaving an abasic site
after base is cleaved, backbone is cleaved
DNA pol and ligase repair region

Question 3

Nucleotide Excision Repair (NER)

Answer 3

repairs bulky lesions (thymine dimers, chemical intercalation)
enzyme recognizes and binds bulky distortion
enzyme nicks DNA around distortion
helicase removes DNA
DNA pol and ligase repair the region

Question 4

Double Strand Break Repair (DSB)

Answer 4

repairs DNA breaks generated by x-rays, reactive oxygen species
non-homologous end joining and homology directed repair

Question 5

Non-Homologous End Joining (NHEJ)

Answer 5

error-prone
occurs mostly during G1
proteins recognize break and rejoin the ends of the chromosomes, this usually introduces small insertions/deletions and therefore frequent frameshift mutations

Question 6

Homology Directed Repair (HDR)

Answer 6

error free repair
occurs mostly in S phase
similar to crossing over
proteins recognize the break, chew away 5’ end to create 3’ overhangs, one of the overhangs base pairs with a homologous region on the homologous chromosome, HDR enzymes use the homologous chromosome as a template to synthesize the region of DNA spanning the double strand break

Question 7

Translesion Synthesis

Answer 7

enables a cell to replicate its DNA and divide even if it has un-repaired lesions
results in permanent incorporation of mutations into the DNA
regular DNA pol synthesizes DNA and falls off when it encounters a lesion, a special error-prone DNA pol comes in and synthesizes DNA through the lesion, guesses what nucleotides it should incorporate while using lesion-containing DNA strand as a template

Question 8

Xeroderma Pigmentosum

Answer 8

caused by NER enzyme mutations
cannot repair UV radiation damage (thymine dimers)
exposure to sunlight can cause fatal cancers

Question 9

Fragile X Syndrome

Answer 9

expansion of repetitive sequences in the promoter region
length of a repeat sequence on FMR-1 gene associated with severity of the condition
lots of CG makes it overmethylated, causing a decrease in gene expression

Question 10

Huntington’s Disease

Answer 10

expansion of repetitive DNA sequences in protein coding regions
expanded repeat of CAG allele, long region of DNA sequence that can be difficult to replicate, often adds repeats
at some point, so many repeats that the protein becomes nonfunctional (causing HD)