High-Resolution Holocene Alluvial Chronostratigraphy at Archaeological Sites in Eastern Grand Canyon, Arizona

Understanding the nature of Colorado River deposits in Grand Canyon helps reveal how the river responds to changes in its Colorado Plateau tributaries and Rocky Mountain headwaters. This study focused on Holocene alluvial deposits associated with archaeological sites excavated near Ninemile Draw in Glen Canyon and at Tanner Bar in eastern Grand Canyon. Two previously-developed conceptual models of deposition were tested based on previous work. Previous researchers have suggested that Holocene alluvial deposits in Grand Canyon are a series of inset aggradational packages that correlate to valley fills and arroyo-cutting cycles in Colorado Plateau tributaries and are laterally consistent throughout the river corridor. An alternate hypothesis is that alluvial packages record paleoflood sequences along the Colorado River with no Holocene change in river grade. In this model, deposits are preserved more variably as a function of local hydrologic geometry, and they should be less correlatable. Detailed stratigraphic columns of terrace deposits and several stratigraphic panels of archaeological trenches, combined with facies interpretations, were used to reconstruct a high-resolution alluvial history at two locations. Optically stimulated luminescence (OSL) and radiocarbon dating methods were used at both locations with consistent results. At both sites, the sediment includes multiple depositional facies of mainstem and local-source material, and it consists of stratal packages bound by unconformities. These stratigraphic relations, combined with geochronology, lead to the interpretation that the alluvium is composed of six correlatable alluvial packages at overlapping heights above river level throughout the canyon. The four older packages include facies that imply aggradation throughout the river corridor, suggesting oscillations in river grade. The youngest two packages consist only of mainstem flood deposits. These packages suggest that preservation of deposits over the past ~1 ky has not been driven by aggradation, although incision since ~1 ky is possible. Comparison of the interpreted chronostratigraphy to climate records suggests that this large river\u27s grade has not responded visibly to smaller century to millennial-scale climate oscillations. This work is the first to document that the alluvial record in Grand Canyon spans the entire Holocene, and conclusions support to both previous conceptual models of deposition

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

Using DNA-modified electrodes, we show DNA-mediated signaling by XPD, a helicase that contains a [4Fe-4S] cluster and is critical for nucleotide excision repair and transcription. The DNA-mediated redox signal resembles that of base excision repair proteins, with a DNA-bound redox potential of ~80 mV versus NHE. Significantly, this signal increases with ATP hydrolysis. Moreover, the redox signal is substrate-dependent, reports on the DNA conformational changes associated with enzymatic function, and may reflect a general biological role for DNA charge transport

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

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 redox-active [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 DNA-bound 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

MRE11 facilitates the removal of human topoisomerase II complexes from genomic DNA

Topoisomerase II creates a double-strand break intermediate with topoisomerase covalently coupled to the DNA via a 5'-phosphotyrosyl bond. These intermediate complexes can become cytotoxic protein-DNA adducts and DSB repair at these lesions requires removal of topoisomerase II. To analyse removal of topoisomerase II from genomic DNA we adapted the trapped in agarose DNA immunostaining assay. Recombinant MRE11 from 2 sources removed topoisomerase IIalpha from genomic DNA in vitro, as did MRE11 immunoprecipitates isolated from A-TLD or K562 cells. Basal topoisomerase II complex levels were very high in A-TLD cells lacking full-length wild type MRE11, suggesting that MRE11 facilitates the processing of topoisomerase complexes that arise as part of normal cellular metabolism. In K562 cells inhibition of MRE11, PARP or replication increased topoisomerase IIalpha and beta complex levels formed in the absence of an anti-topoisomerase II dru

Surgeons or Scribes? The Role of United States Court of Appeals Law Clerks in Appellate Triage

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Surgeons or Scribes? The Role of United States Court of Appeals Law Clerks in Appellate Triage

Using original survey data, we explore how federal courts of appeals judges select and use their law clerks—a question that we answered in an earlier article about federal district court clerks. As with that first article, we do not intend to tackle such normative issues as whether courts of appeals law clerks possess too much influence over the judicial process or whether the selection criteria used by these judges is appropriate. What we will present, however, is descriptive data on the criteria that courts of appeals judges use to pick their law clerks as well as the tasks assigned to those clerks. We believe that our findings, namely, that courts of appeals judges delegate substantial job duties to their clerks, should serve as the springboard for a future debate over the wisdom of such delegation

Translocation and deletion breakpoints in cancer genomes are associated with potential non-B DNA-forming sequences

Gross chromosomal rearrangements (including translocations, deletions, insertions and duplications) are a hallmark of cancer genomes and often create oncogenic fusion genes. An obligate step in the generation of such gross rearrangements is the formation of DNA double-strand breaks (DSBs). Since the genomic distribution of rearrangement breakpoints is non-random, intrinsic cellular factors may predispose certain genomic regions to breakage. Notably, certain DNA sequences with the potential to fold into secondary structures [potential non-B DNA structures (PONDS); e.g. triplexes, quadruplexes, hairpin/cruciforms, Z-DNA and single-stranded looped-out structures with implications in DNA replication and transcription] can stimulate the formation of DNA DSBs. Here, we tested the postulate that these DNA sequences might be found at, or in close proximity to, rearrangement breakpoints. By analyzing the distribution of PONDS-forming sequences within ±500 bases of 19 947 translocation and 46 365 sequence-characterized deletion breakpoints in cancer genomes, we find significant association between PONDS-forming repeats and cancer breakpoints. Specifically, (AT)n, (GAA)n and (GAAA)n constitute the most frequent repeats at translocation breakpoints, whereas A-tracts occur preferentially at deletion breakpoints. Translocation breakpoints near PONDS-forming repeats also recur in different individuals and patient tumor samples. Hence, PONDS-forming sequences represent an intrinsic risk factor for genomic rearrangements in cancer genomes