Physicochemical Mechanism of Light-Driven DNA Repair by (6-4) Photolyases

Faraji, Shirin; Dreuw, Andreas

doi:10.1146/annurev-physchem-040513-103626

Cited by 47 publications

(89 citation statements)

References 81 publications

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“…Also, a two-photon repair mechanism has been proposed [110, 111]. Various theoretical calculations were carried out and several repair models have been suggested [104, 107–109, 112, 113]. Most of these proposed models invoke one proton transfer from a neighboring histidine residue at the active site (Fig.…”

Section: (6-4) Photoproduct Repair and Photocyclementioning

confidence: 99%

Photolyase: Dynamics and electron-transfer mechanisms of DNA repair

Zhang

Wang

Zhong

2017

Archives of Biochemistry and Biophysics

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Photolyase, a flavoenzyme containing flavin adenine dinucleotide (FAD) molecule as a catalytic cofactor, repairs UV-induced DNA damage of cyclobutane pyrimidine dimer (CPD) and pyrimidine-pyrimidone (6-4) photoproduct using blue light. The FAD cofactor, conserved in the whole protein superfamily of photolyase/cryptochromes, adopts a unique folded configuration at the active site that plays a critical functional role in DNA repair. Here, we review our comprehensive characterization of the dynamics of flavin cofactor and its repair photocycles by different classes of photolyases on the most fundamental level. Using femtosecond spectroscopy and molecular biology, significant advances have recently been made to map out the entire dynamical evolution and determine actual timescales of all the catalytic processes in photolyases. The repair of CPD reveals seven electron-transfer (ET) reactions among ten elementary steps by a cyclic ET radical mechanism through bifurcating ET pathways, a direct tunneling route mediated by the intervening adenine and a two-step hopping path bridged by the intermediate adenine from the cofactor to damaged DNA, through the conserved folded flavin at the active site. The unified, bifurcated ET mechanism elucidates the molecular origin of various repair quantum yields of different photolyases from three life kingdoms. For 6-4 photoproduct repair, a similar cyclic ET mechanism operates and a new cyclic proton transfer with a conserved histidine residue at the active site of (6-4) photolyases is revealed.

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Section: (6-4) Photoproduct Repair and Photocyclementioning

confidence: 99%

Photolyase: Dynamics and electron-transfer mechanisms of DNA repair

Zhang

Wang

Zhong

2017

Archives of Biochemistry and Biophysics

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“…Persistence of these lesions can interfere with essential processes such as transcription and DNA replication leading to mutation, nucleotide misincorporation and eventually to cell death. In fact, (6‐4) photoproducts are supposed to be the major players in the formation of skin cancer . To maintain genetic integrity, many organisms have developed an elegant mechanism to repair these lesions using photo‐activated enzymes called DNA photolyases .…”

Section: Figurementioning

confidence: 99%

Characterization of the Intermediate in and Identification of the Repair Mechanism of (6‐4) Photolesions by Photolyases

2016

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Quantum mechanics/molecular mechanics calculations are employed to assign previously recorded experimental spectroscopic signatures of the intermediates occurring during the photo-induced repair of (6-4) photolesions by photolyases to specific molecular structures. Based on this close comparison of experiment and theory it is demonstrated that the acting repair mechanism involves proton transfer from the protonated His365 to the N3′ nitrogen of the lesion, which proceeds simultaneously with intramolecular OH transfer along an oxetane-like transition state.

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“…At the molecular level, ultraviolet light irradiation generates dimers between two adjacent pyrimidine residues in nucleotide strands, referred to as cyclobutane pyrimidine dimers [27]. We used an antibody specific for the cyclobutane pyrimidine dimer to detect their presence [28].…”

Section: Resultsmentioning

confidence: 99%

An optical labeling-based proliferation assay system reveals the paracrine effect of interleukin-6 in breast cancer

Itou¹,

Tanaka²,

Sato³

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Proliferation analysis is one of the basic approaches to characterize various cell types. In conventional cell proliferation assays, the same sample cannot be observed over time, nor can a specific group within a heterogeneous population of cells, for example, cancerous cells, be analyzed separately. To overcome these limitations, we established an optical labeling-based proliferation assay system with the Kaede protein, whose fluorescence can be irreversibly photoconverted from green to red by irradiation. After a single non-toxic photoconversion event, the intensity of red fluorescence in each cell is reduced by cell division. From this, we developed a simple method to quantify cell proliferation by monitoring reduction of red fluorescence over time. This study shows that the optical labeling-based proliferation assay is a viable novel method to analyze cell proliferation, and could enhance our understanding of mechanisms regulating cell proliferation machinery. We used this newly established system to analyze the functions of secreted interleukin-6 (IL-6) in cancer cell proliferation, which had not been fully characterized. Reduction in proliferation was observed following IL-6 knockdown. However, after co-culturing with IL-6-expressing cells, the proliferation of Kaede-labeled IL-6-knockdown cells was restored. These data indicate that in basal-like breast cancer cells, IL-6 exhibits a paracrine effect to positively regulate cell proliferation. Our results thus demonstrate that cancer cells can secrete signaling molecules, such as IL-6, to support the proliferation of other cancer cells.

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Physicochemical Mechanism of Light-Driven DNA Repair by (6-4) Photolyases

Cited by 47 publications

References 81 publications

Photolyase: Dynamics and electron-transfer mechanisms of DNA repair

Photolyase: Dynamics and electron-transfer mechanisms of DNA repair

Characterization of the Intermediate in and Identification of the Repair Mechanism of (6‐4) Photolesions by Photolyases

An optical labeling-based proliferation assay system reveals the paracrine effect of interleukin-6 in breast cancer

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