Search results
Results from the WOW.Com Content Network
Oxygen is a potent radiosensitizer, increasing the effectiveness of a given dose of radiation by forming DNA-damaging free radicals. Tumor cells in a hypoxic environment may be as much as 2 to 3 times more resistant to radiation damage than those in a normal oxygen environment. [5]
Radiolysis of intracellular water by ionizing radiation creates peroxides, which are relatively stable precursors to hydroxyl radicals. 60%–70% of cellular DNA damage is caused by hydroxyl radicals, [3] yet hydroxyl radicals are so reactive that they can only diffuse one or two molecular diameters before reacting with cellular components.
After DNA damage, cell cycle checkpoints are activated. Checkpoint activation pauses the cell cycle and gives the cell time to repair the damage before continuing to divide. DNA damage checkpoints occur at the G1/S and G2/M boundaries. An intra-S checkpoint also exists. Checkpoint activation is controlled by two master kinases, ATM and ATR.
[3] [4] Later, by characterizing the phenotypes of mutagenised E. coli, she and post doctoral student Miroslav Radman detailed the SOS response to UV radiation in bacteria. [3] [5] The SOS response to DNA damage was a seminal discovery because it was the first coordinated stress response to be elucidated. [6]
Nucleotide excision repair (NER) is a particularly important excision mechanism that removes DNA damage induced by ultraviolet light (UV). UV DNA damage results in bulky DNA adducts — these adducts are mostly thymine dimers and 6,4-photoproducts. Recognition of the damage leads to removal of a short single-stranded DNA segment that contains ...
Conversely, certain bacteria utilize photolyase, powered by sunlight, to repair pyrimidine dimer-induced DNA damage. Unrepaired lesions may lead to erroneous nucleotide incorporation by polymerase machinery. Overwhelming DNA damage can precipitate mutations within an organism's genome, potentially culminating in cancer cell formation. [7]
The former is very damaging to DNA, while the latter events create clusters of DNA damage. [38] [39] This damage includes loss of nucleobases and breakage of the sugar-phosphate backbone that binds to the nucleobases. The DNA organization at the level of histones, nucleosomes, and chromatin also affects its susceptibility to radiation damage. [40]
Damage to DNA that occurs naturally can result from metabolic or hydrolytic processes. Metabolism releases compounds that damage DNA including reactive oxygen species, reactive nitrogen species, reactive carbonyl species, lipid peroxidation products, and alkylating agents, among others, while hydrolysis cleaves chemical bonds in DNA. [8]