dna damage and repair Flashcards
mutation
accidental change in the sequence of bases in the genome; result from DNA damage that is an ongoing threat to the cell; some DNA damage is spontaneous, but DNA is often caused by environmental factors
deamination of ______ and _________ occur spontaneously in a human cell. deamination of __ and __ also occurs spontaneously but at a slower rate. Some common chemicals can accelerate the rate of deamination, such as __________ and ____________
C->U and 5meC->T; A and G; sodium nitrite and sodum nitrate
__________ in the genome are permanent and are subsequently inherited by daughter cells
mutations
______________________ are generated by respiration
- hydroxide free radical inserts into either G or T
- oxidation can result in DNA strand breaks
reactive oxygen species (ROS)
_____________ is caused by hydrolysis of the N-B-glycosyl bond linking a purine base to the sugar-phosphate backbone.
- yields an _________ site or _____ site
depurination; abasic; AP
_____________ covalently modify bases in DNA.
- distorts the DNA double helix
alkylation
ultraviolent radiation is a common cause of DNA damage
- UV results in the formation of a cyclobutane ring between two adjacent pyrimidine rings
- this is especially common for pairs of thymines forming a _____________
- the cyclobutane ring kinks the axis of the DNA helix
thymine-dimer
_____________ causes DNA strand breakage.
major sources of ______________ are cosmic rays, X-rays, and radioactive materials.
radiation can cause either:
- __________________
-__________________
- damaged bases at break sites
ionizing radiation; ionizing radiation; single strand break; double strand break
in higher eukaryotes, the transcription factor _____ is key to DNA repair by activating genes involved in cell cycle arrest, DNA repair, and apoptosis.
- guardian of the genome
- kinases phosphorylate ___, which increases its transcriptional activity
- ataxia telanglectasia mutated (ATM) gene
p53
most DNA repair mechanisms can be broken down into four distinct phases:
1) recognition of the lesion
2) excision of the lesion
3) resynthesis of the DNA
4) ligation of loose ends
________________ corrects mismatched base pairs from errors in replication
mismatch repair (MMR)
prokaryotic MMR proteins:
- ___________ complex recognizes the mismatch
- _______ identifies the parental GAmeTC strand and newly synthesized strand
- MutH endonuclease nicks the unmethylated strand
- an _____________ digests from the nick through the mismatch making a gap in the unmethylated strand
- ________ fills the gap
- ________ seals the nick
*eukaryotes have homologous MMR proteins
MutL-MutS; MutH; exonuclease; DNA pol III; DNA ligase
______________ repairs mismatches resulting from damaged bases, depurination, and single strand breaks in DNA.
base excision repair
A ______________ cleaves the N-B-glycosyl bond making an __________ site (AP site)
- abasic sites arise from activity of a DNA glycosylase or depurination
- _______________ initiates repair of abasic sites by making a single strand break in DNA at the abasic site
- __________ has both the 5’->3’ exonuclease and the DNA synthesis activities
- high fidelity polymerase
- in eukaryotes, _________ serves this purpose
- ___________ seals the nick
DNA glycosylase; abasic site; AP endonuclease; DNA pol I; DNA pol B; DNA ligase
prokaryotic nucleotide excision repair
- repairs lesions that distort the DNA double helix, such as thymine dimers or alkylation
- ________________ makes two nicks in the damaged strand flanking the lesion
- ______________ excises the damaged DNA leaving a gap
- __________ fills the gap
- __________ seals the nick
uvrABC excinuclease; uvrD helicase; DNA pol I; DNA ligase
