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Base excision repair capacity in informing healthspan

Published on Dec 1, 2014in Carcinogenesis4.004
· DOI :10.1093/carcin/bgu225
Boris M. Brenerman3
Estimated H-index: 3
(NIH: National Institutes of Health),
Jennifer L. Illuzzi6
Estimated H-index: 6
(NIH: National Institutes of Health),
David M. Wilson49
Estimated H-index: 49
(NIH: National Institutes of Health)
Abstract
Base excision repair (BER) is a frontline defense mechanism for dealing with many common forms of endogenous DNA damage, several of which can drive mutagenic or cell death outcomes. The pathway engages proteins such as glycosylases, abasic endonucleases, polymerases and ligases to remove substrate modifications from DNA and restore the genome back to its original state. Inherited mutations in genes related to BER can give rise to disorders involving cancer, immunodeficiency and neurodegeneration. Studies employing genetically defined heterozygous (haploinsufficient) mouse models indicate that partial reduction in BER capacity can increase vulnerability to both spontaneous and exposure-dependent pathologies. In humans, measurement of BER variation has been imperfect to this point, yet tools to assess BER in epidemiological surveys are steadily evolving. We provide herein an overview of the BER pathway and discuss the current efforts toward defining the relationship of BER defects with disease susceptibility.
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