Abstract
Retinitis pigmentosa (RP) is a genetically heterogeneous disease characterized by degeneration of the retina. Mutations in the RP2 gene are linked to the second most frequent form of X-linked retinitis pigmentosa. RP2 is a plasma membrane-associated protein of unknown function. The N-terminal domain of RP2 shares amino acid sequence similarity to the tubulin-specific chaperone protein co-factor C. The C-terminus consists of a domain with similarity to nucleoside diphosphate kinases (NDKs). Human NDK1, in addition to its role in providing nucleoside triphosphates, has recently been described as a 3' to 5' exonuclease. Here, we show that RP2 is a DNA-binding protein that exhibits exonuclease activity, with a preference for single-stranded or nicked DNA substrates that occur as intermediates of base excision repair pathways. Furthermore, we show that RP2 undergoes re-localization into the nucleus upon treatment of cells with DNA damaging agents inducing oxidative stress, most notably solar simulated light and UVA radiation. The data suggest that RP2 may have previously unrecognized roles as a DNA damage response factor and 3' to 5' exonuclease.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Active Transport, Cell Nucleus / physiology
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Active Transport, Cell Nucleus / radiation effects
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Cell Nucleus / genetics
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Cell Nucleus / metabolism
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DNA Damage / physiology*
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DNA Damage / radiation effects
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DNA Repair / genetics*
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DNA Repair / radiation effects
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DNA, Single-Stranded / genetics
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DNA, Single-Stranded / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / radiation effects
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Exodeoxyribonucleases / genetics
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Exodeoxyribonucleases / metabolism*
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Exodeoxyribonucleases / radiation effects
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Eye Proteins / genetics
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Eye Proteins / metabolism*
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Eye Proteins / radiation effects
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GTP-Binding Proteins
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HeLa Cells
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Humans
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Mutation / physiology
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Mutation / radiation effects
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Oxidative Stress / drug effects
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Oxidative Stress / genetics
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Pigment Epithelium of Eye / cytology
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Pigment Epithelium of Eye / metabolism*
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Pigment Epithelium of Eye / radiation effects
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Protein Transport / physiology
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Protein Transport / radiation effects
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Retinitis Pigmentosa / enzymology*
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Retinitis Pigmentosa / genetics
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Retinitis Pigmentosa / physiopathology
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Ultraviolet Rays
Substances
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DNA, Single-Stranded
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DNA-Binding Proteins
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Eye Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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RP2 protein, human
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Exodeoxyribonucleases
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GTP-Binding Proteins