DNA Replication, Repair, and Mutagenesis Flashcards
origin of replication
initiation sites for DNA replication
T-ag (T-antigen)
viral protein needed for eukaryotic “model system” studies, also a helicase
helicase
enzyme that disrupts hydrogen bonds of dsDNA
RPA
Human single stranded binding protein
Bloom’s Syndrome
Disease in which helicase is deficient; high risk of developing malignancies (leukemia)
Werner’s Syndrome
Disease in which a helicase is defective, causes premature aging
DNA primase
Synthesizes RNA primer to initiate replication
pol alpha-primase complex
Synthesizes DNA primer, necessary to initiate transcription
Pol epsilon
DNA polymerase that adds nucleotides to the leading strand
Pol delta
DNA polymerase that adds nucleotides to the lagging strand
PCNA
Proliferating Cell Nuclear Antigen - clamps the polymerases to the DNA
RFC
Replication Factor C - loads polyermases onto the DNA
Okazaki fragments
lagging strand fragments of DNA
DNA ligase
covalently links the Okazaki fragments of the lagging strand
Acyclovir
inhibits DNA polymerase encoded by herpes simplex virus but termination replication
AZT (Azidothymidine)
inhibits reverse transcriptase encoded by HIV
kinases
enzymes that add phosphate groups to other molecules
cyclin/cyclin dependent kinases
important in regulating the cell cycle
p53 protein
prevents cells from dividing if they have damaged DNA, if mutated, cancer can result
mismatch repair
mechanism for removing incorrect bases in DNA
Mut S
recognizes DNA mismatch
Mut H
catalyzes DNA strand incision for mismatch repair
Mut L
Thought to provide a protein-protein interface for mismatch repair
Trinucleotide repeats
repeating sequences of three nucleotides that can lead to disease, stabilized by mismatch repair pathways
excision repair
removal of a faulty DNA segment by DNA synthesis
uvrABC
recognizes and cleaves damaged DNA strand of pyrimidine dimer in excision repair
xerderma pigmentosum
disease from biochemical defects of excision repair process
Li-Fraumeni Syndrome
individuals with mutant p53, can’t arrest cell cycle if DNA is damaged
Hereditary non-polyposis colon cancer (HNPCC)
mutations in mismatch repair genes leads to a predisposition to cancers
Fragile X Syndrome, Myotonic Dystrophy, Huntingtons Disease
trinucleotide repeat disorders
uracil-DNA glycosidase
removes inappropriate uracil, leaving AP site
deamination
cytosine converts to uracil OR adenine converts to hypoxanthine (G)
methylation
leads to loss of guanine residue due to labilization of N-glycosidic linkage
intercaltors
get between bases of DNA, disturb double helical structure
examples of intercaltors
ethidium bromide, proflain, acridine orange