ATP-Stimulated, DNA-Mediated Redox Signaling by XPD, a DNA Repair and Transcription Helicase

Mui, Timothy P.; Fuss, Jill O.; Ishida, Justin P.; Tainer, John A.; Barton, Jacqueline K.

doi:10.1021/ja207222t

Cited by 53 publications

(107 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Electrochemical studies have shown that when BER proteins MutY and EndoIII bind to DNA, their [4Fe-4S] clusters are activated toward one electron oxidation (14,26). XPD exhibits a DNA-bound midpoint potential similar to that of EndoIII and MutY when bound to DNA (approximately 80 mV vs. NHE), indicative of a possible role for the [4Fe-4S] cluster in DNA-mediated CT (34). For EndoIII we have also already determined a direct correlation between the ability of proteins to redistribute in the vicinity of mismatches as measured by AFM, and the CT proficiency of the proteins measured electrochemically (23).…”

Section: Discussionmentioning

confidence: 99%

“…Protein concentrations were determined using the UV-visible absorbance of the [4Fe-4S] cluster (410 nm, ε ¼ 17;000) (55). XPD was purified as previously described (34).…”

Section: Methodsmentioning

confidence: 99%

“…Protein electrochemistry was performed as previously described (34). Briefly, individual proteins samples were dialyzed to remove residual DTT and quantified based on 410 nm absorbance.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

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.

Self Cite

127

View full text Add to dashboard Cite

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

show abstract

Section: Discussionmentioning

confidence: 99%

“…Protein concentrations were determined using the UV-visible absorbance of the [4Fe-4S] cluster (410 nm, ε ¼ 17;000) (55). XPD was purified as previously described (34).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

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.

Self Cite

127

View full text Add to dashboard Cite

show abstract

“…126 Like small molecule redox probes, the integrity of the DNA π -stack is critical for strong electrochemical signals from these proteins; the incorporation of intervening abasic sites, lesions, or mismatches in the DNA electrode significantly attenuate the redox signal. 126-129 …”

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.

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Therefore, it is important to understand how inter-individual variations in the DNA sequence of specific genes affect the response to environmental genotoxic agents. Takanami et al (2005) cycle Ito et al, 2010;Li et al, 2010;Mui et al, 2011). Similarly, the functional difference of ERCC2/XPD protein may alter the modulation of the whole XPB-XPD-CAK chain in cells.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

The ERCC2/XPD Lys751Gln polymorphism affects DNA repair of benzo[a]pyrene induced damage, tested in an in vitro model

Xiao

Cui

et al. 2016

Toxicology in Vitro

View full text Add to dashboard Cite

ATP-Stimulated, DNA-Mediated Redox Signaling by XPD, a DNA Repair and Transcription Helicase

Cited by 53 publications

References 27 publications

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

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

The ERCC2/XPD Lys751Gln polymorphism affects DNA repair of benzo[a]pyrene induced damage, tested in an in vitro model

Contact Info

Product

Resources

About