DNA-mediated redox signaling for transcriptional activation of SoxR

Lee, Paul E.; Demple, Bruce; Barton, Jacqueline K.

doi:10.1073/pnas.0906429106

Cited by 53 publications

(51 citation statements)

References 35 publications

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“…Another possible role for the 2Fe-2S cluster of CPSF30 is to regulate oligonucleotide binding a redox-dependent manner; Fe-S clusters are emerging as key cofactors in a range of regulatory proteins. In some proteins for which the Fe-S cluster plays a regulatory role, such as the base excision repair proteins, the Fe-S cluster's DNA binding affinity is dependent on the oxidation state of the Fe-S cluster and modulated by DNA charge transfer (57)(58)(59)(60)(61)(62). In others, such as Aft2 (which also contains a structural zinc site), it is the presence or absence of the Fe-S cluster that drives DNA binding (63).…”

Section: Discussionmentioning

confidence: 99%

Cleavage and polyadenylation specificity factor 30: An RNA-binding zinc-finger protein with an unexpected 2Fe–2S cluster

Shimberg

Michalek

Oluyadi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cleavage and polyadenylation specificity factor 30 (CPSF30) is a key protein involved in pre-mRNA processing. CPSF30 contains five Cys 3 His domains (annotated as "zinc-finger" domains). Using inductively coupled plasma mass spectrometry, X-ray absorption spectroscopy, and UV-visible spectroscopy, we report that CPSF30 is isolated with iron, in addition to zinc. Iron is present in CPSF30 as a 2Fe-2S cluster and uses one of the Cys 3 His domains; 2Fe-2S clusters with a Cys 3 His ligand set are rare and notably have also been identified in MitoNEET, a protein that was also annotated as a zinc finger. These findings support a role for iron in some zinc-finger proteins. Using electrophoretic mobility shift assays and fluorescence anisotropy, we report that CPSF30 selectively recognizes the AU-rich hexamer (AAUAAA) sequence present in pre-mRNA, providing the first molecular-based evidence to our knowledge for CPSF30/RNA binding. Removal of zinc, or both zinc and iron, abrogates binding, whereas removal of just iron significantly lessens binding. From these data we propose a model for RNA recognition that involves a metaldependent cooperative binding mechanism.zinc | iron-sulfur | RNA | protein | binding

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Section: Discussionmentioning

confidence: 99%

Cleavage and polyadenylation specificity factor 30: An RNA-binding zinc-finger protein with an unexpected 2Fe–2S cluster

Shimberg

Michalek

Oluyadi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Indeed, XPD may utilize DNA-mediated CT to signal its presence and perhaps to "call off" other proteins from other repair pathways. Various DNA-binding proteins, such as those involved in repair and other DNA transactions, have been found to contain iron-sulfur domains and other redox cofactors (50)(51)(52)(53). DNAmediated signaling among DNA-binding proteins that are involved in maintaining the integrity of the genome allows a coordination of repair, transcription, and replication processes.…”

Section: Discussionmentioning

confidence: 99%

DNA charge transport as a first step in coordinating the detection of lesions by repair proteins

Sontz

Mui

Fuss

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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127

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Damaged bases in DNA are known to lead to errors in replication and transcription, compromising the integrity of the genome. We have proposed a model where repair proteins containing redoxactive [4Fe-4S] clusters utilize DNA charge transport (CT) as a first step in finding lesions. In this model, the population of sites to search is reduced by a localization of protein in the vicinity of lesions. Here, we examine this model using single-molecule atomic force microscopy (AFM). XPD, a 5′-3′ helicase involved in nucleotide excision repair, contains a [4Fe-4S] cluster and exhibits a DNAbound redox potential that is physiologically relevant. In AFM studies, we observe the redistribution of XPD onto kilobase DNA strands containing a single base mismatch, which is not a specific substrate for XPD but, like a lesion, inhibits CT. We further provide evidence for DNA-mediated signaling between XPD and Endonuclease III (EndoIII), a base excision repair glycosylase that also contains a [4Fe-4S] cluster. When XPD and EndoIII are mixed together, they coordinate in relocalizing onto the mismatched strand. However, when a CT-deficient mutant of either repair protein is combined with the CT-proficient repair partner, no relocalization occurs. These data not only indicate a general link between the ability of a repair protein to carry out DNA CT and its ability to redistribute onto DNA strands near lesions but also provide evidence for coordinated DNA CT between different repair proteins in their search for damage in the genome.DNA electron transfer | iron-sulfur clusters | oxidative damage

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“…130 This important shift maintains the protein in an inactive state during normal conditions such that it only becomes activated when the cell experiences conditions of high oxidative stress. Proper coupling to the DNA π -stack is additionally important for this protein, as solution experiments have shown that SoxR can be activated from a distance by DNA CT. 134 Clearly, as in the case of small molecule redox probes, strong electronic coupling to the DNA π -stack is essential to produce measurable electrochemical signals. For proteins like SoxR, however, this coupling has an added level of significance, as it can actually modulate the redox character of the protein itself, significantly impacting the function of the protein in a biological context.…”

Section: Dna Ct On Surfacesmentioning

confidence: 99%

Solution, surface, and single molecule platforms for the study of DNA-mediated charge transport

Muren

Olmon

Barton

2012

Phys. Chem. Chem. Phys.

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The structural core of DNA, a continuous stack of aromatic heterocycles, the base pairs, which extends down the helical axis, gives rise to the fascinating electronic properties of this molecule that is so critical for life. Our laboratory and others have developed diverse experimental platforms to investigate the capacity of DNA to conduct charge, termed DNA-mediated charge transport (DNA CT). Here, we present an overview of DNA CT experiments in solution, on surfaces, and with single molecules that collectively provide a broad and consistent perspective on the essential characteristics of this chemistry. DNA CT can proceed over long molecular distances but is remarkably sensitive to perturbations in base pair stacking. We discuss how this foundation, built with data from diverse platforms, can be used both to inform a mechanistic description of DNA CT and to inspire the next platforms for its study: living organisms and molecular electronics.

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DNA-mediated redox signaling for transcriptional activation of SoxR

Cited by 53 publications

References 35 publications

Cleavage and polyadenylation specificity factor 30: An RNA-binding zinc-finger protein with an unexpected 2Fe–2S cluster

Cleavage and polyadenylation specificity factor 30: An RNA-binding zinc-finger protein with an unexpected 2Fe–2S cluster

DNA charge transport as a first step in coordinating the detection of lesions by repair proteins

Solution, surface, and single molecule platforms for the study of DNA-mediated charge transport

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