Ayooshi Mitra, Amity University Kolkata
A genomic study of skin cells shows that there is a wide range of age-independent mutations in the normal number of somatic mutations that arise from exposure to UV light. The human skin is constantly subjected to damage of DNA due to the environment, which leads to the accumulation of somatic mutations over an individual’s lifetime. In human skin cells, mutagenesis can also be caused by endogenous DNA damage and errors in DNA replication. During this study, the researchers sequenced genomes from single cell-derived clonal lineages obtained from primary skin cells from an outsized cohort of healthy individuals over a good range of ages and reported the range of mutation load and a comprehensive view of the various somatic genome changes that accumulate in skin cells.
The research published in PLOS Genetics on 14th January, also confirms that darker skin is more protected from UV-related mutations, something scientists have long suspected of. According to Saini N, one must understand what a normal cancer genome is, before saying that cancer genomes have either more or fewer mutations or even anything different from normal. The study also showed that even in sun-shielded skin, UV-induced base substitutions, insertions, and deletions are prominent. Also, mutation accumulation due to spontaneous methylated cytosine deamination as well as insertions and deletions characteristic of DNA replication errors are detected in these cells. Potent sources of gross chromosomal rearrangements in human cells are DNA replication stalling at common fragile sites. Thus, the interaction of environmental and endogenous factors in facilitating genome instability and carcinogenesis is reflected by somatic mutations in the skin of healthy individuals.
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Reference:
- Saini N, Giacobone CK, Klimczak LJ, Papas BN, Burkholder AB, Li J-L, et al. (2021) UV-exposure, endogenous DNA damage, and DNA replication errors shape the spectra of genome changes in human skin. PLoS Genet 17(1): e1009302. https://doi.org/10.1371/journal.pgen.1009302
Link for article: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009302
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