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In humans and other mammals, DNA damage occurs frequently and DNA repair processes have evolved to compensate. [11] In estimates made for mice, DNA lesions occur on average 25 to 115 times per minute in each cell, or about 36,000 to 160,000 per cell per day. [12] Some DNA damage may remain in any cell despite the action of repair processes.
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]
A major challenge in bisulfite sequencing is the degradation of DNA that takes place concurrently with the conversion. The conditions necessary for complete conversion, such as long incubation times, elevated temperature, and high bisulfite concentration, can lead to the degradation of about 90% of the incubated DNA. [27]
Purine degradation takes place mainly in the liver of humans and requires an assortment of enzymes to degrade purines to uric acid. First, the nucleotide will lose its phosphate through 5'-nucleotidase. The nucleoside, adenosine, is then deaminated and hydrolyzed to form hypoxanthine via adenosine deaminase and
The telomeres are long regions of repetitive noncoding DNA that cap chromosomes and undergo partial degradation each time a cell undergoes division (see Hayflick limit). [14] In contrast, quiescence is a reversible state of cellular dormancy that is unrelated to genome damage (see cell cycle).
Typical DNA methylation landscape in mammals. The DNA methylation landscape of vertebrates is very particular compared to other organisms. In mammals, around 75% of CpG dinucleotides are methylated in somatic cells, [19] and DNA methylation appears as a default state that has to be specifically excluded from defined locations.
DNase I cleaves DNA to form two oligonucleotide-end products with 5’-phospho and 3’-hydroxy ends and is produced mainly by organs of the digestive system. The DNase I family requires Ca2+ and Mg2+ cations as activators and selectively expressed. [1] In terms of pH, the DNAses I family is active in normal pH of around 6.5 to 8.
Most organisms have the same genomic DNA in every cell; however, only certain genes are active in each cell to allow for cell function and differentiation within the body. [2] gDNA predominantly resides in the cell nucleus packed into dense chromosome structures. Chromatin refers to the combination of DNA and proteins that make up chromosomes.