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1.
Biochemistry ; 52(51): 9275-85, 2013 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-24328089

RESUMO

The cis-syn thymine cyclobutane dimer is a DNA photoproduct implicated in skin cancer. We compared the stability of individual base pairs in thymine dimer-containing duplexes to undamaged parent 10-mer duplexes. UV melting thermodynamic measurements, CD spectroscopy, and 2D NOESY NMR spectroscopy confirm that the thymine dimer lesion is locally and moderately destabilizing within an overall B-form duplex conformation. We measured the rates of exchange of individual imino protons by NMR using magnetization transfer from water and determined the equilibrium constant for the opening of each base pair K(op). In the normal duplex K(op) decreases from the frayed ends of the duplex toward the center, such that the central TA pair is the most stable with a K(op) of 8 × 10⁻7. In contrast, base pair opening at the 5'T of the thymine dimer is facile. The 5'T of the dimer has the largest equilibrium constant (K(op) = 3 × 10⁻4) in its duplex, considerably larger than even the frayed penultimate base pairs. Notably, base pairing by the 3'T of the dimer is much more stable than by the 5'T, indicating that the predominant opening mechanism for the thymine dimer lesion is not likely to be flipping out into solution as a single unit. The dimer asymmetrically affects the stability of the duplex in its vicinity, destabilizing base pairing on its 5' side more than on the 3' side. The striking differences in base pair opening between parent and dimer duplexes occur independently of the duplex-single strand melting transitions.


Assuntos
Dano ao DNA , DNA de Forma B/química , Modelos Moleculares , Oligodesoxirribonucleotídeos/química , Dímeros de Pirimidina/química , Pareamento de Bases , Fenômenos Bioquímicos , Dicroísmo Circular , DNA de Forma B/metabolismo , Medição da Troca de Deutério , Cinética , Ressonância Magnética Nuclear Biomolecular , Conformação de Ácido Nucleico , Desnaturação de Ácido Nucleico , Oligodesoxirribonucleotídeos/metabolismo , Prótons , Dímeros de Pirimidina/metabolismo , Estereoisomerismo
2.
Appl Opt ; 51(29): 7069-79, 2012 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-23052087

RESUMO

We present flight results from the optical pointing control system onboard the Planetary Imaging Concept Testbed Using a Rocket Experiment (PICTURE) sounding rocket. PICTURE (NASA mission number: 36.225 UG) was launched on 8 October 2011, from White Sands Missile Range. It attempted to directly image the exozodiacal dust disk of ϵ Eridani (K2V, 3.22 pc) down to an inner radius of 1.5 AU using a visible nulling coronagraph. The rocket attitude control system (ACS) provided 627 milliarcsecond (mas) RMS body pointing (~2'' peak-to-valley). The PICTURE fine pointing system (FPS) successfully stabilized the telescope beam to 5.1 mas (0.02λ/D) RMS using an angle tracker camera and fast steering mirror. This level of pointing stability is comparable to that of the Hubble Space Telescope. We present the hardware design of the FPS, a description of the limiting noise sources and a power spectral density analysis of the FPS and rocket ACS in-flight performance.

3.
Appl Opt ; 51(15): 2877-87, 2012 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-22614589

RESUMO

Complementary metal-oxide semiconductor (CMOS)-hybrid arrays have become competitive optical detectors for use in ground- and space-based astronomy. Interpixel capacitance (IPC) is one source of error that appears in most CMOS arrays. In this paper, we use a single-pixel-reset method to model IPC. We combine this IPC model with a model for charge diffusion to estimate the total crosstalk on H4RG-10 arrays. Finally, we compare our model results to 55Fe data obtained using an astrometric camera built to test the H4RG-10 B0 generation detectors.

4.
Biochemistry ; 50(39): 8463-77, 2011 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-21902242

RESUMO

The base lesion 8-oxoguanine is formed readily by oxidation of DNA, potentially leading to G → T transversion mutations. Despite the apparent similarity of 8-oxoguanine-cytosine base pairs to normal guanine-cytosine base pairs, cellular base excision repair systems effectively recognize the lesion base. Here we apply several techniques to examine a single 8-oxoguanine lesion at the center of a nonpalindromic 15-mer duplex oligonucleotide in an effort to determine what, if anything, distinguishes an 8-oxoguanine-cytosine (8oxoG-C) base pair from a normal base pair. The lesion duplex is globally almost indistinguishable from the unmodified parent duplex using circular dichroism spectroscopy and ultraviolet melting thermodynamics. The DNA mismatch-detecting photocleavage agent Rh(bpy)(2)chrysi(3+) cleaves only weakly and nonspecifically, revealing that the 8oxoG-C pair is locally stable at the level of the individual base pairs. Nuclear magnetic resonance spectra are also consistent with a well-conserved B-form duplex structure. In the two-dimensional nuclear Overhauser effect spectra, base-sugar and imino-imino cross-peaks are strikingly similar between parent and lesion duplexes. Changes in chemical shift due to the 8oxoG lesion are localized to its complementary cytosine and to the 2-3 bp immediately flanking the lesion on the lesion strand. Residues further removed from the lesion are shown to be unperturbed by its presence. Notably, imino exchange experiments indicate that the 8-oxoguanine-cytosine pair is strong and stable, with an apparent equilibrium constant for opening equal to that of other internal guanine-cytosine base pairs, on the order of 10(-6). This collection of experiments shows that the 8-oxoguanine-cytosine base pair is incredibly stable and similar to the native pair.


Assuntos
Pareamento de Bases , Dano ao DNA , Guanina/análogos & derivados , Oligodesoxirribonucleotídeos/química , Sequência de Bases , Dano ao DNA/efeitos dos fármacos , Reparo do DNA , Guanina/síntese química , Guanina/química , Espectroscopia de Ressonância Magnética , Termodinâmica
5.
Appl Opt ; 43(11): 2316-24, 2004 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-15098834

RESUMO

We have made simultaneous and nearly simultaneous measurements of L0, the outer scale of turbulence, at the Palomar Observatory by using three techniques: angle-of-arrival covariance measurements with the Generalized Seeing Monitor (GSM), differential-image-motion measurements with the adaptive-optics system on the Hale 5-m telescope, and fringe speed measurements with the Palomar Testbed Interferometer (PTI). The three techniques give consistent results, an outer scale of approximately 10-20 m, despite the fact that the spatial scales of the three instruments vary from 1 m for the GSM to 100 m for the PTI.

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