Dna Repair Enzymes

Sancar, Aziz; Sancar, Gwendolyn B.

doi:10.1146/annurev.bi.57.070188.000333

Cited by 811 publications

(460 citation statements)

References 58 publications

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“…A spectral characterization of the UVA light source indicated that ~60% fell within the range of 365 ± 8 nm (USB2000 spectrometer, Ocean Optics, Dudedin, FL). The output of this UVA source is similar to that known to activate photolyases across various terrestrial and aquatic organisms' systems [24], with the exception that longer wavelength (e.g., photosynthetically active radiation) contribution here was minimal. The UVA source was chosen primarily for its ability to photoactivate caged compounds, where longer wavelengths are not as effective [25].…”

Section: Ultraviolet Radiation Exposurementioning

confidence: 51%

“…The broad output in the UVB region (shown in Supplemental Data, Fig. S1) matches the absorbance spectra of the many targets affecting cellular processes, such as DNA, cell membranes, and proteins [23], and in particular, the CPDs that are corrected in photorepair [24]. Ultraviolet radiation A (UVA) was supplied with a high intensity (GreenSpot 100-Watt) super pressure mercury lamp with a 5 × 1000 mmlight guide (American Ultraviolet, Lebanon, IN), which provided an irradiance at 4.2 cm of 0.705 W/cm 2 at 365 nm with short bandpass and infrared filters.…”

Section: Ultraviolet Radiation Exposurementioning

confidence: 99%

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Photobiological effects of UVA and UVB light in zebrafish embryos: Evidence for a competent photorepair system

Dong

Svoboda

Tiersch

et al. 2007

Journal of Photochemistry and Photobiology B: Biology

110

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The consequences of UVB and UVA irradiation on hatch rate, mortality, and malformation were studied in embryonic zebrafish (Danio rerio). The use of zebrafish embryos has expanded from traditional developmental models to diverse studies, including many techniques utilizing light exposure. To characterize useful indicators of photodamage, the responses and threshold limits of UV radiation as a function of embryonic stage and fish source were evaluated. Significant differences in UVB susceptibility were observed in embryos at 3, 6-7, 12, and 24 h postfertilization (hpf), with the 1000-cell stage (3 hpf) having greatest tolerance to UVB. Embryos derived from zebrafish raised in outdoor ponds were more tolerant to UVB than were embryos from laboratory-raised fish. Combinations of UVB and UVA exposure were used to confirm the presence of a competent photorepair system in zebrafish that could return otherwise malformed embryos to a normal phenotype. Overall, embryonic zebrafish had large tolerances (LD 50 of 850 J/cm 2 ) to UVA, confirming their suitability for photoactivation and photorepair studies.

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Section: Ultraviolet Radiation Exposurementioning

confidence: 51%

Section: Ultraviolet Radiation Exposurementioning

confidence: 99%

Photobiological effects of UVA and UVB light in zebrafish embryos: Evidence for a competent photorepair system

Dong

Svoboda

Tiersch

et al. 2007

Journal of Photochemistry and Photobiology B: Biology

110

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“…Unlike restriction enzymes that cleave the DNA in the sugar phosphate backbone, the CPD photolyase directly removes the cross-linking of adjacent pyrimidines in the CPD photolesions such as T-T 28 . Structural studies have revealed that DDB2 has a protein fold that flips out and maintains contact with T-T 26 , and our results indicate that PARP-1 also remains in the vicinity of T-T lesion.…”

Section: No Effect Of Parp-1 and Ddb2 Binding On Cpd-photolyase Mediamentioning

confidence: 99%

Characterization of the interactions of PARP-1 with UV-damaged DNA in vivo and in vitro

Purohit

Robu

Shah

et al. 2016

Sci Rep

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The existing methodologies for studying robust responses of poly (ADP-ribose) polymerase-1 (PARP-1) to DNA damage with strand breaks are often not suitable for examining its subtle responses to altered DNA without strand breaks, such as UV-damaged DNA. Here we describe two novel assays with which we characterized the interaction of PARP-1 with UV-damaged DNA in vivo and in vitro. Using an in situ fractionation technique to selectively remove free PARP-1 while retaining the DNA-bound PARP-1, we demonstrate a direct recruitment of the endogenous or exogenous PARP-1 to the UV-lesion site in vivo after local irradiation. In addition, using the model oligonucleotides with single UV lesion surrounded by multiple restriction enzyme sites, we demonstrate in vitro that DDB2 and PARP-1 can simultaneously bind to UV-damaged DNA and that PARP-1 casts a bilateral asymmetric footprint from −12 to +9 nucleotides on either side of the UV-lesion. These techniques will permit characterization of different roles of PARP-1 in the repair of UV-damaged DNA and also allow the study of normal housekeeping roles of PARP-1 with undamaged DNA.The abundance of poly (ADP-ribose) polymerase-1 (PARP-1) in mammalian cells and its rapid catalytic activation to form polymers of ADP-ribose (PAR) in the presence of various types of DNA damages with or without strand breaks has made it an ideal first responder at the lesion site to influence downstream events 1,2 . Apart from DNA damages, PARP-1 is also recruited to DNA during normal physiological processes such as transcription and chromatin remodeling 3 , which do not involve overt DNA damage but just altered DNA structures. While we know much more about how PARP-1 rapidly recognizes and binds to single or double strand breaks in DNA, we know very little about how PARP-1 interacts with DNA damages or altered DNA structures without strand breaks. The key reason is that the existing methodologies that readily identify interactions of PARP-1 with DNA strand breaks are not sufficiently sensitive to study the relatively weaker responses of PARP-1 to DNA damage without strand breaks. The response of PARP-1 to UVC-induced direct photolesions, such as cyclobutane pyrimidine dimers (CPD) that are formed without any DNA strand breaks exemplifies this problem.Recent studies from others and our team have shown the involvement of PARP-1 in the host cell reactivation 4 and specifically in the nucleotide excision repair (NER) of UV-damaged DNA through its interaction with early NER protein DDB2 [5][6][7] . Additional studies have shown that downstream NER proteins XPA 8,9 and XPC 10 are PARylated. Thus, PARP-1 possibly has multiple roles in NER, but we do not yet fully understand its interactions with UV-damaged DNA or other NER proteins due to two major challenges. The first challenge is that unlike for many NER proteins, the abundance of endogenous PARP-1 in the nucleus makes it nearly impossible to visualize its dynamics of recruitment to UV-damaged DNA in situ using conventional immunocytological methods. T...

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“…This kind of DNA repair is initiated by DNA glycosylases, enzymes that recognize the modified bases and act by cleaving the glycosylic bond, thereby removing the damaged base from the sugar phosphate backbone and, as a result, producing an apurinic/apyrimidinic (AP) site (Sancar and Sancar, 1988).…”

Section: Dna Repair Pathways and Antioxidant Defense Systems Base Excmentioning

confidence: 99%

Several pathways of hydrogen peroxide action that damage the E. coli genome

Asad

Almeida

et al. 2004

Genet. Mol. Biol.

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Hydrogen peroxide is an important reactive oxygen species (ROS) that arises either during the aerobic respiration process or as a by-product of water radiolysis after exposure to ionizing radiation. The reaction of hydrogen peroxide with transition metals imposes on cells an oxidative stress condition that can result in damage to cell components such as proteins, lipids and principally to DNA, leading to mutagenesis and cell death. Escherichia coli cells are able to deal with these adverse events via DNA repair mechanisms, which enable them to recover their genome integrity. These include base excision repair (BER), nucleotide excision repair (NER) and recombinational repair. Other important defense mechanisms present in Escherichia coli are OxyR and SosRS anti-oxidant inducible pathways, which are elicited by cells to avoid the introduction of oxidative lesions by hydrogen peroxide. This review summarizes the phenomena of lethal synergism between UV irradiation (254 nm) and H 2 O 2 , the cross-adaptive response between different classes of genotoxic agents and hydrogen peroxide, and the role of copper ions in the lethal response to H 2 O 2 under low-iron conditions. Key words: hydrogen peroxide, cross-adaptive response, lethal synergism, copper and iron. General AspectsThe appearance of aerobic forms of life was an important step in the evolutionary process, since oxygen consumption leads to the production of ten-fold more energy from glucose than does anaerobic metabolism (Meneghini, 1987). However, this process imposes constraints on cell viability, because of the generation of reactive oxygen species during respiration.The consecutive univalent reduction of molecular oxygen to water produces three active intermediates: superoxide anion (O 2 -• ), hydrogen peroxide (H 2 O 2 ) and hydroxyl radical (OH • ). These intermediates, collectively referred to as reactive oxygen species (ROS) are potent oxidants of lipids, proteins, and nucleic acids (Halliwell and Gutteridge, 1984;Mello-Filho and Meneghini, 1985;Meneghini, 1988). Among the oxidative DNA lesions, one of the major classes of DNA damage leads to modification in purine and pyrimidine bases, together with oligonucleotide strand breaks, DNA-protein cross-links and abasic sites. Increasing evidence suggests that the cumulative damage caused by ROS contributes to numerous degenerative diseases associated with aging, such as atherosclerosis, rheumatoid arthritis and cancer (Ames et al., 1993;Halliwell and Gutteridge, 1999).Living organisms have developed specific mechanisms to prevent the production and effects of ROS. The reduction of O 2 by cytochrome oxidase without yielding ROS, the superoxide dismutase catalysis of O 2 -• into H 2 O 2 through a dismutation reaction, the decomposition of H 2 O 2 by catalase and peroxidases, and the scavenging of ROS by some vitamins comprise part of the set of cellular antioxidant defenses (Halliwell and Gutteridge, 1999). Synthesis of the enzymes that catalyze these reactions is a part of the adaptive response tr...

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Dna Repair Enzymes

Cited by 811 publications

References 58 publications

Photobiological effects of UVA and UVB light in zebrafish embryos: Evidence for a competent photorepair system

Photobiological effects of UVA and UVB light in zebrafish embryos: Evidence for a competent photorepair system

Characterization of the interactions of PARP-1 with UV-damaged DNA in vivo and in vitro

Several pathways of hydrogen peroxide action that damage the E. coli genome

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