Lect. 4 - DNA replication, repair and recomb 2 Flashcards
(17 cards)
What type of damaged DNA needs repaired?
DNA damaged from replication errors and also from accidental lesions that occur in the genome
how many accidental base changes result in a permanent mutation?
fewer than 1/1000
Spontaneous DNA damage
mutations aren’t only caused by mistakes in replication
5000 purine bases are lost every day due to a spontaneous reaction called?
depurination - hydrolysis of the n-glycosyl linkage
Deamination
C to U - occurs at 100 bases/day
DNA damage
can also occur from exposure to reactive forms of O2 in the cell or chemicals in environment
UV radiation damage
can produce a covalent linkage b/w 2 adjacent pyrimidines (T-T or C-T) ; pyrimidines dimers (will distort the backbone of the DNA)
What happens if the DNA damage is unrepaired when the DNA is replicated?
The changes lead to either a deletion or base pair substitution in the daughter strand
DNA glycosylases (in BER)
- at least 6 different types
- each recognizes a specific type of altered base and catalyzes its removal
AP endonuclease and phosphodiesterase (in BER)
cut phosphodiester backbone; damage is removed and gap is repaired
in BER, how are depurinations repaired?
directly repaired beginning w/ AP endonuclease
Nucleotide Excision Repair (NER)
differs from BER in how damage is removed; can repair any bulky lesion like those chemically-induced and thymine dimers (anything that distorts the DNA)
NER process
- a multienzyme complex scans DNA for distortion in double helix instead of specific base change
- cleaves phophodiester backbone on both sides; DNA helicase peels lesion-containing strand away
In NER, what is the large gap repaired by?
DNA polymerase and ligase
Transcription-coupled repair
works w/ BER, NER and others to repair genes that are being expressed when the damage occurs; cells can preferentially direct DNA repair to sequences that are being actively transcribed by linking RNA polymerase 2/ DNA repair; sequences that urgently need repair
RNA polymerase in TCR
RNA polymerase stalls at lesions and directs repair machinery there
TCR is specific for the strand being transcribed
non-transcribed strand repaired at the same rate as DNA not being transcribed