DNA mutations and repair Flashcards
what is the nature of a mutation
errors can arise during DNA replication; failure to repair lesions results in a mutation which alter the sequence of bases in a gene.
whats the diff bet a mutation in prokaryotes vs eukaryotes
- for prokaryotes a mutation affects the only copy of the genetic info available and passes it to the next generation.
- eukaryotes; somatic mutations can affect tissues but are not heritable. Mutations in germ cells that predispose to cancer can be inherited.
Somatic mutations are ___, many mutations have minimal effect. and initially only one cell is affected. Somatic mustions are only harmful if they result in a ____of mutant cells
inevitable; clone
Turning a normal cell into a malignant cancer cell requires ___specific mutations in one cell
6
what are four major types of mutations
- Substitution
- Deletion
- Insertion
- Rearrangement
- deletions, insertions and rearrangements often occur together
what are the types of substitution (point) mutations
- silent: no change in aa
- missense: change in aa
- nonsense: change in DNA makes change in mRNA which intro termination codon, you get shorter protein
- frameshift: delete/insert one of the bases that change everything from there on
what is a transition substitution
purine for purine, pyrimidine for pyrimidine
what is a trasversion substitution
purine for pyrimidine, or pyrimidine for purine
what is the most common mutation in cystic fibrosis
deletion of one codon (for phenylalanine)
What are causes of mutations
- Errors during DNA replication: tautomer formation causes substitution
- Chemical modification: mutagens causes substitution
- intercalation: of chemical mutagens bet bases cause insertions or deletions
- double strand breakage: radiation, certain mutagens causes rearrangements and deletions
Nitrous acid reacts with ___containg amino groups and causes oxidative deamination and can result in AT–>GC transitions.
bases
bases are not 100% stable; spontaneous ____modifications can occur
chemical
mustard gas is considered an alkylating agent which donates alkyl groups to bases and changes pairing properties of base by:
adds carbs to base which changes pairing properties
What can intercalation cause
Introduces an obstacel to replication; Distorts how DNA looks and can block DNA resplication and RNA transcription
what can radiation cause
Xray exposure causes DS breaks in DNA resulting in rearrangements, deletion. UV exposure causes thymine dimers that interfere with replication
what are mutation repair systems
- Mismatch repair; mostly due to tautomer formation
- Base excision repair; looks for abnormal bases
- nucleotide excision repair; large structure changes
- direct repair; repair single base
how do the enzymes for base excision repair work
take out base and leave sugar backbone which leaves AP site rec by endonucleases which cleave DNA from that site with DNA polymerase 1 and DNA ligase
whats a pattern seen in mutation repair enzymes
Recognition, excision, and repair
whats special about ABC exinuclase
recognition and excision from same enzyme
whats special about O6 methylguanine DNA methyltransferase
takes methyl group off guanine (to own specific cysteine) and accept it on methyltransferase enzyme
In E.Coli there are enzymes that detect mismatch:
MutS: detects mismatch
MutL: complexes with mismatch
MutH; recognizes sequence that is methylated
how does mismatch repair occur in E. coli
Parent strand seps; hemimethylated state at GATC sites which can be rec by MutH which will cleave unmethylated seq. Fill it with Dna pol III and seal with ligase
what does defect in human mismatch repair system lead to:
hereditary nonpolyposis colorectal cancer
All cells have ___ ____ that remove abnormal bases in a DNA strand from their attached sugar and leave AP site. specific ___ ___ cuts sugar out and repair system fills in gap
DNA glycosylases; AP endonucleases
In humans, defect of the human thymine dimer repair system leads to autosomal recessive disease called
xeroderma pigemntosum; ind have high sensitivity to skin damage by UV light and strong predisposition to skin cancer.
Direct repair is more efficient. ___ dimers can be repaired by light induced reverse reaction catalyzed by ____
pyrimidine; photolyases
what is the process affected and phenotype of hereditary nonpolyposis colorectal cancer
mismatch repair; colon cancer
what is the process affected and phenotype of xeroderma pigmentosum
nucleotide excision repair; skin cancer, UV sensitivity, neurological defects.
