Lect. 4 - DNA replication, repair and recomb 2 Flashcards
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
