Stem cells are often referred to as the mother of all cells, meaning that they sit at the apex of a cellular hierarchy and, upon differentiation, give rise to all the mature cells of a tissue. DNA damage constantly arises from DNA replication, spontaneous chemical reactions and assaults by external or metabolism-derived agents. Therefore, all living cells must constantly contend with DNA damage. It is particularly crucial for survival of organisms how DNA damage is handled in stem cells, including tissue specific stem cells. While tissue-specific stem cells share the same purpose of maintaining organ functionality, recent studies have shown that the mechanisms of their response to DNA damage, the outcome of their DNA damage response, and the consequence of DNA repair for genomic stability vary greatly between tissues. Striking differences in the outcome of DNA damage response (DDR) have been seen in hematopoietic stem cells from different species and at different developmental stages. Furthermore cell cycle and metabolic states of stem cells seem to affect choices of DNA repair pathways and a choice between cell survival and death.
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