Lecture 4 Flashcards
Mutations doe not only occure because of mistakes in replication
spontaneous DNA damage
What needs to be repaired in DNA
replications errors
accidental lesions
What is the spontaneous reaction to which 5000 purines are lost every day?
depurination
hydrolysis of the N-glycosyl linkage
What spontaneously occurs with 100 C to U bases/ day?
damination
What is caused by UV readation from the sun, or chemicals in the environment?
Produce a covalent linakge btw two adjacent pyrimidines (T-T) or (C-T)
purimidine dimers
What if DNA goes unrepaired?
deletion or base pair substitution in the duaghter strand
Base excision repair
Takes out the base, small repair
BER, six different types
- each recognizes a specific type of altered base and catalyzes its removal
DNA glycosylases
BER… Enzyme probes for damage by…
flipping out of base from helix to check if it is correct
BER, What happens if DNA glycosylases find an incorrect base?
cleaves glycosyl bond connecting base w sugar
BER What cuts the phosphodiester backbone to remove and repair gap?
AP endonuclease and phosphodiesterase
BER what are directly reapired begging w AP endonuclease?
depurinations
BER What adds new nucleotides/
DNA polymerase
What seals nick in DNA
DNA ligase
nucleotide excision repair…
repairs any bulky lesion like those chemically induced and thymine dimers
How does NER work?
a multienzyme complex scans DNA for distortion in double helix instead of specific base change
What does NER cleave?
phosphodiester backbone on both sides; DNA helicase peels lesion containg strand away
With NER what is the large gap repaired by?
DNA polymerase and ligase
Transcription coupled repair
cells can preferentially direct DNA repair to sequences that are being actively transcribed by linking RNA polymerase with DNA repair
- sequences that urgentyl need repair
TCR repairs by?
RNA plymerase stalls at lesions and directs repair machinery there
How does TCR work with BER, NER and others to repair genes?
Repairs genes that are being expressed when the damage occurs
What is TCR specific too?
the strand being transcribed
TCR
Non- transcribed strand repaired at the same rate as DNA not being trnascribed
- defect in transcritipon coupled repair
- growth retardation, skeletal abnormalitites, sensitivty to light
- RNA polymerase is permanetely stalled at sites of damage in importnat genes
Cockayne’s syndrome