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Concept
ADN polymérase bêta
Résumé
DNA polymerase beta, also known as POLB, is an enzyme present in eukaryotes. In humans, it is encoded by the POLB gene.
In eukaryotic cells, DNA polymerase beta (POLB) performs base excision repair (BER) required for DNA maintenance, replication, recombination, and drug resistance.
The mitochondrial DNA of mammalian cells is constantly under attack from oxygen radicals released during ATP production. Mammalian cell mitochondria contain an efficient base excision repair system employing POLB that removes some frequent oxidative DNA damages. POLB thus has a key role in maintaining the stability of the mitochondrial genome.
An analysis of the fidelity of DNA replication by polymerase beta in the neurons from young and very aged mice indicated that aging has no significant effect on the fidelity of DNA synthesis by polymerase beta. This finding was considered to provide evidence against the error catastrophe theory of aging.
Cabelof et al. measured the ability to repair DNA damage by the BER pathway in tissues of young (4-month-old) and old (24-month-old) mice. In all tissues examined (brain, liver, spleen and testes) the ability to repair DNA damage declined significantly with age, and the reduction in repair capability correlated with decreased levels of DNA polymerase beta at both the protein and messenger RNA levels. Numerous investigators have reported an accumulation of DNA damage with age, especially in brain and liver. Cabelof et al. suggested that the inability of the BER pathway to repair damages over time may provide a mechanistic explanation for the frequent observations of DNA accumulation of damage with age.
DNA polymerase beta maintains genome integrity by participating in base excision repair. Overexpression of POLB mRNA has been correlated with a number of cancer types, whereas deficiencies in POLB results in hypersensitivity to alkylating agents, induced apoptosis, and chromosomal breaking. Therefore, it is essential that POLB expression is tightly regulated.
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