Lecture 9 Flashcards
When do mutations most commonly occur?
During DNA replication
What strand breakage is most commonly induced by radiation?
Double strand breaks
What percentage of DNA mutations are repaired by repair pathways?
99%
What does strand slippage cause?
Mutations via insertions/deletions of base pairs
Where do strand slippage mutations most commonly occur?
Areas of repeated DNA
What type of virus requires integration into host chromosomes?
Retrovirus
What are transposons?
Inherited DNA sequences that can cut and paste themselves from one location to another in the genome
What type of DNA are transposons?
Repetitive
How can transposons lead to cancer?
Overproduction of oncogene proteins by insertional activation
Alu transposon insertion results in what two cancers?
Neurofibromatosis type 1 and bladder carcinoma
Transposon miso airing can cause
Unequal crossing over, deletion/duplication
What are the five types of DNA repair?
Direct repair, base excision repair, nucleotide excision repair, mismatch repair, and recombinational repair
Which type of DNA repair deals with broad class helix-distorting lesions that disrupt transcription and replication?
Nucleotide excision repair (NER)
Which repair pathway deals with small chemical alterations if bases and is particularly important for preventing mutation?
Base excision repair (BER)
Which repair pathway corrects replication errors and can repair alkylated bases?
Mismatch repair (MMR)
Which repair pathway includes homologous recombination (HR) and non-homologous end joining (NHEJ)?
Double-strand break (DSB) repair
What are the four steps of nucleotide excision repair?
Dual incision of unwound DNA on both sides of lesion, excision of damaged DNA, repair by polymerization, ligation
What are the two subpathways of NER?
Global genome repair (GGR) and transcription coupled repair (TCR)
Where does GGR function?
Entire genome
Where does TCR function?
Lesions specifically blocking transcription
Which DNA repair pathway is important for fixing UV damage?
Nucleotide excision repair (NER)
What are the three genetic disorders causes by mutated NER?
Xeroderma Pigmentosum (XP), Cockayne’s Syndrome (CS), and TrichoThioDystrophy (TTD)
What are four types of base damage that base excision repair is responsible for fixing?
Oxidative lesions, alkylation products, bulky DNA adducts, and base hydrolysis
What enzyme removes uracil from the DNA?
Uracil-DNA glycosylase (UNG/UDG)
How dose base excision repair (BER) work?
Single nucleotide is excised, DNA polymerase β fills gap, DNA ligase III seals gap
What protein is responsible for the recognition of abnormal DNA bass?
DNA glycosylase
What does DNA glycosylase do once it recognizes and binds DNA at abnormal site?
Hydrolytically cleaves base off sugar backbone, creating an AP site (apurine/apyrimidine)
What are three important AP endonucleases?
hAPE, hAP1, REF1
Direct reversal DNA repair is responsible for what?
Dealkylating affected bases
