Protamine-Induced Condensation and Decondensation of the Same DNA Molecule

Brewer, Laurence R.; Corzett, Michele; Balhorn, Rod

doi:10.1126/science.286.5437.120

Cited by 248 publications

(228 citation statements)

References 22 publications

(7 reference statements)

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“…They showed that DNA condenses continuously and linearly with time once the compaction process begins. [14][15][16][17] The results seemed to support the widely accepted opinion that the toroid is formed by continuously absorbing DNA to a primary loop randomly nucleated on DNA. The temporal resolution of the experiments was, however, relatively low.…”

supporting

confidence: 75%

Compaction Dynamics of Single DNA Molecules under Tension

Wang

Zhang

et al. 2006

J. Am. Chem. Soc.

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The compaction of DNA by multivalent cations has been the subject of many investigations, not only because it is biologically important, but also because it poses a fascinating challenge to our understanding of semiflexible polymers. [1][2][3][4][5] Polyelectrolyte theory has figured out that the attractive potential that leads to DNA compaction originates from correlated fluctuation of counterions shared between DNA segments. 6 Experimental observations have revealed that DNA condensates have generally a toroidal geometry with a typical size of ∼100 nm in diameter. It is generally believed that DNA within a toroid is organized in a hexagonal close-packed lattice, 7 but how such a structure is formed is still not fully understood.Single-molecule measurements have proven helpful to understanding the nucleation and growth of DNA condensates. [8][9][10][11][12][13] A few recent experiments concentrated on the kinetics of DNA compaction. They showed that DNA condenses continuously and linearly with time once the compaction process begins. [14][15][16][17] The results seemed to support the widely accepted opinion that the toroid is formed by continuously absorbing DNA to a primary loop randomly nucleated on DNA. The temporal resolution of the experiments was, however, relatively low. They might not be able to resolve the time trajectories of the DNA compaction.Exerting forces on DNA is a useful way to study processes relevant to DNA. 18 The force may slow down the dynamical process so that details can be observed using an apparatus of finite temporal resolution. Here we report single-molecule studies on the dynamics of hexaammine cobalt chloride-induced DNA compaction under tension. It turns out that the compaction process is more sophisticated than the static structural model has suggested. DNA condenses into toroid in a quantized manner.The measurements were performed using transverse magnetic tweezers similar to the one recently developed by Yan and Marko. 19 Two micrometer-sized beads are tethered to the two ends of a λ-phage DNA (16.4 µm). One bead is fixed in space by a micropipette, and the other is free in solution. A magnetic rod is inserted into the solution to generate a constant force to the free magnetic bead. The experiments were done in phosphate-buffered saline (10 mM PBS, 5 mM NaCl, pH ) 7.4). After adjusting the force on DNA, 10 µL of 10 mM hexaammine cobalt chloride solution was added into the sample cell. The final concentration of the trivalent cations was 100 µM. Figure 1a shows the time course of DNA compaction at a force F ) 0.5 pN. Time courses measured at other concentrations of the trivalent cations (from 35 to 200 µM) are quite similar. After addition of the cations, a long induction period was observed before the compaction started. The induction time becomes longer when a less concentrated solution of trivalent cations is added. The compaction is discontinuous and stepwise. The two big steps in Figure 1a consist of multiple small steps. Such discontinuous compactions were also observed...

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supporting

confidence: 75%

Compaction Dynamics of Single DNA Molecules under Tension

Wang

Zhang

et al. 2006

J. Am. Chem. Soc.

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“…Therefore the intensity of fluorescence is low in sperm as compared to fluorescence intensity of round spermatid [66][67][68].…”

Section: Basics Of Dna Integrity Assaysmentioning

confidence: 99%

Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility

Shamsi

Imam

Dada

2011

J Assist Reprod Genet

135

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Sperm is not a simple carrier of paternal genetic information but its role extends clearly beyond fertilization. Integrity of sperm genome is an essential pre-requisite for birth of healthy offspring and evaluation of sperm should entail DNA integrity analysis. DNA integrity analysis is a better diagnostic and prognostic marker of sperm reproductive potential. Conventional semen analysis emphasizes on sperm concentration, viability, motility and morphology and has been proven to be a poor indicator of reproductive potential and pregnancy outcome. To overcome the drawbacks associated with conventional semen analysis more useful fertility tests and molecular biomarkers have been explored. Among the different tests which have evolved for assessing the sperm reproductive potential, tests for sperm DNA quality are most promising. Sperm DNA damage has been closely associated with numerous indicators of reproductive health including fertilization, embryo quality, implantation, spontaneous abortion, congenital malformations and childhood diseases. It therefore has great potential as a prognostic test for both in vitro and in vivo conception. This review presents an updated account of tests that have better diagnostic and prognostic implications in the evaluation of sperm DNA damage. The basic principles, outline of methodology, advantage, disadvantage, clinical significance of each technique and implications of these tests have been discussed. The logistics of each test with respect to available resources and equipment in an andrology laboratory, the feasibility of performing these tests in routine diagnostic workup of infertile men and the opportunities and challenges provided by DNA testing in male fertility determination are also presented.

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“…Dox/Duplex was mixed with m-protamine at an optimal mass ratio of 14:17 to prepare a positively charged Dox-loaded complex 41 (Dox/Complex) ( Fig. 3a and Supplementary Fig.…”

mentioning

confidence: 99%

ATP-triggered anticancer drug delivery

et al. 2014

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Stimuli-triggered drug delivery systems have been increasingly used to promote physiological specificity and on-demand therapeutic efficacy of anticancer drugs. Here we utilize adenosine-5'-triphosphate (ATP) as a trigger for the controlled release of anticancer drugs. We demonstrate that polymeric nanocarriers functionalized with an ATP-binding aptamer-incorporated DNA motif can selectively release the intercalating doxorubicin via a conformational switch when in an ATP-rich environment. The half-maximal inhibitory concentration of ATP-responsive nanovehicles is 0.24 mM in MDA-MB-231 cells, a 3.6-fold increase in the cytotoxicity compared with that of non-ATP-responsive nanovehicles. Equipped with an outer shell crosslinked by hyaluronic acid, a specific tumour-targeting ligand, the ATP-responsive nanocarriers present an improvement in the chemotherapeutic inhibition of tumour growth using xenograft MDA-MB-231 tumour-bearing mice. This ATP-triggered drug release system provides a more sophisticated drug delivery system, which can differentiate ATP levels to facilitate the selective release of drugs.

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Protamine-Induced Condensation and Decondensation of the Same DNA Molecule

Cited by 248 publications

References 22 publications

Compaction Dynamics of Single DNA Molecules under Tension

Compaction Dynamics of Single DNA Molecules under Tension

Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility

ATP-triggered anticancer drug delivery

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