28 Flashcards
(44 cards)
DSB
double stranded breaks
what causes DSB
principle cytotoxic lesion for ionizing radiation and radio mimetic chemicals
or mechanical stress on chromosomes or when DNA pol encounters DNA ss break or other type of DNA lesion
inaccurate repair of these can lead to mutations or genomic instability
tumorgenic potential
can induce appoptosis
occur as intermediates in biological events just as V(D)J recombination in developing lymphoid cells
DSB
mechanisms for repairing dsDNA breaks
non homologous end joinign (NHEJ)
homology directed repair- gene conversion
homology directed repair- homologous recombination
dna seq info copies from one place to another
homology directed repair- gene conversion
dna segments are exchagned
homology directed repair- homologous recombination
exchanges DNA
rseutls in new genetic combinations in meiosis, conjugation, transduction, and transformation
homologous remcombination
copies DNA from elsewhere in the genome
homology directed repair
any mechanism of recombination has to include the followign
DNA synth
generation of regions of heteroduplex DNA
what initiates homologous recombination and homology directed repari
ds break and resection
what causes ds breaks
endonucleases or damage
yeas ds break
HO endonuclease
removal of DNA in one strand due to action of 5’-3’ exonuclease
resection
bacteria resection
RecBCD
yeast resection
MRX exonuclease
human resection
MRN econuclease
what binds to single starnd ends
strand exchange recombinases
strand exchange recombinases examples
RecA (bact)
Rad51(Euk)
Dmc(meiosis specific)
what do recombinase bound single strands do
invade the homologous duplex (second copy of molecule )
forms D loop
leaving us with a substrate for DNA synth
DNA synthesized using invading strand as a primer
what happnes in homologus recombination
unpaired strand in D loop is captured by the othe end of the resectioned break and DNA synth can occur there
POINT OF DIFF BQ GENE CONVERSION AND HOMOLOGOUS RECOMBINATION
outcome of homologous recombination
two intat dsDNA molecules joined by holiday junctions
ways of resolving holiday junctions determine
whether or not recmombination occurs
resolving two junctions in the same direction
no recombination occurs
A and B still on same moecule
heteroduplex non recmbinants are formed
resolving two junctions in different directions
recombinant molecules are generateed
A and B on diffferent moelcuels
heteroduplex recombiannts are formed