Topic 10: DNA damage Flashcards
where is DNA integrity important on what levels
at nucleotide and gene level
at chromosome level - passed on generationally
what two types of damage can be caused
single strand damage (integrity of DNA molecule not affected)
double strand damage (genotoxic)
why are DNA repair mechanisms so important
if not checked - can lead to mutations
what components of the DNA molecule can be damaged
ALL
what are some different types of DNA damage
single strand break base missing chemical changes to bases base into uracil (RNA) pyrimidine diamers formed which have been formed bulky parts added insertion deletion interstrand cross link double stranded break
what sources can cause DNA damage
Exogenous and endogenous
what are some examples of exogenous sources
ionising radiation, UV, alkylating agents, mutagenic chemicals, anti cancer drugs, free radicals
what are free radicals
caused by ionising radiation which damage DNA
also created by mitochondria and white blood cell
what are some examples of endogenous sources
free radicals and replication error
what is DNA replication stress
inefficient replication that leads to replication fork slowing, stalling and or breaking
hoe does DNA replication stress occur
when replication machinery develops a defect, eg: wrong with DNA polymerase
when something hinders the replication fork going forward
when there are defects in response pathway
how does DNA polymerase malfunciton
misincorporation and proofreading of bases
how can DNA polymerase reverse its defect
PROOFREADING- can read back that has made a mistake in incorporating
reverses its movement
3 prime to 5 prime exonuclease activity - take away base
goes in right direction
inserts correct base
what is the function of topoisomerase
releases extra pressure by unwinding DNA further
what can hinder a replication fork
limited number of nucleotides lesions fragile sites insertion of ribonucleotide base DNA loops transcription takes place when not meant to be repetitive DNA
