Changes in DNA repair during aging - PubMed (original) (raw)
Review
Changes in DNA repair during aging
Vera Gorbunova et al. Nucleic Acids Res. 2007.
Abstract
DNA is a precious molecule. It encodes vital information about cellular content and function. There are only two copies of each chromosome in the cell, and once the sequence is lost no replacement is possible. The irreplaceable nature of the DNA sets it apart from other cellular molecules, and makes it a critical target for age-related deterioration. To prevent DNA damage cells have evolved elaborate DNA repair machinery. Paradoxically, DNA repair can itself be subject to age-related changes and deterioration. In this review we will discuss the changes in efficiency of mismatch repair (MMR), base excision repair (BER), nucleotide excision repair (NER) and double-strand break (DSB) repair systems during aging, and potential changes in DSB repair pathway usage that occur with age. Mutations in DNA repair genes and premature aging phenotypes they cause have been reviewed extensively elsewhere, therefore the focus of this review is on the comparison of DNA repair mechanisms in young versus old.
Figures
Figure 1.
Age-related changes in DNA repair and their consequences. Inefficient MMR leads to microsatellite instability, point mutations and potentially, to increased frequency of LOH. Decline in efficiency and fidelity of BER and NER leads to point mutations. Less efficient and more error-prone NHEJ results in point mutations and genomic rearrangements. As fewer cells are in G2 stage, the usage of sub-pathways of DSB repair (DSBR) may also change, where precise HR between sister chromatids declines, giving way to more mutagenic SSA and mitotic recombination (MR) with homologous chromosome leading to genomic instability and LOH.
Figure 2.
The vicious cycle of aging and genomic instability. Spontaneous mutations and rearrangements accumulate with time leading deregulation of transcription, impaired stress response and diminished function of DNA repair genes. Decline of DNA repair efficiency and fidelity leads to more mutations, and further exacerbates the age-related functional decline.
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