3 - DNA Damage and Repair Flashcards
What are mobile genetic elements?
viruses
What is endonuclease?
cuts between phosphodiester bond | cuts DNA
What is glycosylase?
pulls out the bases = separates base from DNA strand
What are the 2 DNA repair pathways for excision repairs?
BER (bases) | NER (nucleotides)
What is the function of methylation?
deactivates gene | happens on specific sites of DNA
What is CpG?
areas in the DNA where Cs and Gs are next to each other
Where in the DNA would methylation ONLY occur?
on a C that is next to a G (CpG)
How likely is demethylation?
rare
Where are CpG islands located?
promoter regions of housekeeping and tissue specific genes
What does CpG-island methylation lead to?
inhibits transcription factors from accessing it bc a bunch of proteins jump onto methylated site = silences gene
How can CpG methylation lead to cancer?
if the wrong genes are silenced/turned off
How can CpG methylation be used as a cancer therapy?
can silence the proto-oncogenes or mutated genes that cause the cell to run wild
What is Base Excision Repair (BER)?
removes the damaged base | more active | transcription-coupled repair pathway
What is Nucleotide Excision Repair (NER)?
removes a stretch of nucleotides | more specific | can be coupled with transcription
What are the enzymes used in BER?
glycosylase, endonuclease, exonuclease, DNA pol beta, ligase
What is the function of glycosylase in the “flipping out” mechanism?
flips one of the bases out and clips it = abasic site
What is the function of endonuclease in the “flipping out” mechanism?
clips on 5’ or 3’ BUT nicks DNA in ine space
Which polymerase fills out the clipped spot from endonuclease in the “flipping out” mechanism?
DNA polymerase beta
What is the function of ligase in the “flipping out” mechanism?
fixes by reforming the phosphodiester bonds
What are scaffolding genes?
proteins that bring in other proteins involved in the DNA repair
What kind of gene are the BRCA1 (breast cancer) genes?
scaffolding genes
What does a mutation in the BRCA1 gene indicate?
something going on in the DNA repair mechanisms
What does NER fix?
thymine dimers | big adducts causing bulky lesions blocking DNA replication
What are the enzymes used in NER?
endonuclease, DNA polymerase, ligase
What is the process for NER?
nick, nick between lesion (endonuclease) »_space;> lift lesion strand out »_space;> fill (DNA polymerase and ligase)
What results from a mutation in a protein involved in the NER pathway?
xeroderma pigmentosum
What is xeroderma pigmentosum?
person sensitive/allergic to UV light = can only come out at night = skin cells cannot repair thymine dimers
What is the difference between xeroderma pigmentosum variant and classical?
biochemical: classical = defect in early step of NER | variant = defect in translesion bypass
What is Trichothiodystrophy?
scaly skin due to dying skin cells from a mutation in one of the parts of the NER mechanism
What are the 5 recombinational DNA repair mechanisms?
daughter strand gap repair | homologous recombination (HR) | non-homologous end-joining (NHEJ) | break-induced repair (BIR) | interstrand-crosslinks
What brings in the BRCA proteins?
checkpoint proteins
What does sporadic mean?
accumulation of mutation throughout our lifetime
What would NHEJ repair mechanism be used for?
if chromosome cannot find its partner | not preferable because results in many mismatches
In NHEJ repair mechanism, how is it trying to fix a mutation?
cell is looking for 2 areas that are closely complimentary = give it enough H-bonds to stick
Why are lesion-replication polymerases error prone to normal DNA?
they have loose specificity
