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A major section of an organism therefore might carry the same mutation, especially if that mutation occurs at earlier stages of development. [2] Somatic mutations that occur later in an organism's life can be hard to detect, as they may affect only a single cell—for instance, a post-mitotic neuron; [3] [4] improvements in single cell ...
Mutations in the DNA damage response genes would appear more likely to act via a second mechanism: allowing for HSC survival and proliferation under normally lethal cytotoxic stress. [1] Other mechanisms are more likely to be associated with the disruption of epigenetic regulators, which comprises 80% of observed mutations in clonal hematopoiesis.
Mutation and DNA damage are the two major types of errors that occur in DNA, but they are fundamentally different. DNA damage is a physical alteration in the DNA structure, such as a single or double strand break, a modified guanosine residue in DNA such as 8-hydroxydeoxyguanosine, or a polycyclic aromatic hydrocarbon adduct. DNA damages can be ...
DNA damage in non-replicating cells, if not repaired and accumulated can lead to aging. DNA damage in replicating cells, if not repaired can lead to either apoptosis or to cancer. The schematic diagram indicates the roles of insufficient DNA repair in aging and cancer, and the role of apoptosis in cancer prevention.
Germline mutations can occur before fertilization and during various stages of zygote development. [3] When the mutation arises will determine the effect it has on offspring. If the mutation arises in either the sperm or the oocyte before development, then the mutation will be present in every cell in the individual's body. [4]
The somatic mutations and epigenetic alterations caused by DNA damage and deficiencies in DNA repair accumulate in field defects. Field defects are normal-appearing tissues with multiple alterations (discussed in the section below), and are common precursors to development of the disordered and over-proliferating clone of tissue in a cancer.
A related theory is that mutation, as distinct from DNA damage, is the primary cause of aging. A comparison of somatic mutation rate across several mammal species found that the total number of accumulated mutations at the end of lifespan was roughly equal across a broad range of lifespans. [49]
The alteration can have direct or indirect effects on the DNA: the induction of mutations, mistimed event activation, and direct DNA damage leading to mutations. The permanent, heritable changes can affect either somatic cells of the organism or germ cells to be passed on to future generations. [1]