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71.
Human MSH2 binds to trinucleotide repeat DNA structures associated with neurodegenerative diseases 总被引:5,自引:5,他引:5
The expansion of trinucleotide repeat sequences is associated with several
neurodegenerative diseases. The mechanism of this expansion is unknown but
may involve slipped-strand structures where adjacent rather than perfect
complementary sequences of a trinucleotide repeat become paired. Here, we
have studied the interaction of the human mismatch repair protein MSH2 with
slipped-strand structures formed from a triplet repeat sequence in order to
address the possible role of MSH2 in trinucleotide expansion. Genomic
clones of the myotonic dystrophy locus containing disease-relevant lengths
of (CTG)n x (CAG)n triplet repeats were examined. We have constructed two
types of slipped-strand structures by annealing complementary strands of
DNA containing: (i) equal numbers of trinucleotide repeats (homoduplex
slipped structures or S-DNA) or (ii) different numbers of repeats
(heteroduplex slipped intermediates or SI-DNA). SI-DNAs having an excess of
either CTG or CAG repeats were structurally distinct and could be separated
electrophoretically and studied individually. Using a band-shift assay, the
MSH2 was shown to bind to both S-DNA and SI-DNA in a structure- specific
manner. The affinity of MSH2 increased with the length of the repeat
sequence. Furthermore, MSH2 bound preferentially to looped-out CAG repeat
sequences, implicating a strand asymmetry in MSH2 recognition. Our results
are consistent with the idea that MSH2 may participate in trinucleotide
repeat expansion via its role in repair and/or recombination.
相似文献
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Edelman RR; Wedeen VJ; Davis KR; Widder D; Hahn P; Shoukimas G; Brady TJ 《Radiology》1986,161(3):779-783
A new technique is described that allows for the creation of pure pulsatile flow magnetic resonance (MR) images in a single acquisition. Five to 16 electrocardiographically gated images spanning the entire cardiac cycle are obtained with use of a gradient-echo pulse sequence. The section can be varied from 4 mm thick to full thickness projection. Taken singly, each image provides direct assessment of flow direction and velocity. Subtraction of image pairs eliminates signal detected from stationary protons, producing images of pulsatile flow. In this study the technique was used to image the flow of cerebrospinal fluid (CSF) in healthy subjects and in one patient with syringohydromyelia. The data suggest that multiphasic MR imaging provides a powerful means for the noninvasive assessment of CSF pulsatile flow dynamics and may have potential clinical application for the investigation of a variety of abnormalities such as normal pressure hydrocephalus, syrinx, and spinal block. 相似文献
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Meuli RA; Wedeen VJ; Geller SC; Edelman RR; Frank LR; Brady TJ; Rosen BR 《Radiology》1986,159(2):411-418
We report the first clinical experience with a new method for projective imaging of blood vessels (angiography) using magnetic resonance. Vascular contrast is produced noninvasively by the phase response of moving protons. Diastolic and systolic gated images produce, respectively, flow signal and flow void; the difference image is a map of the pulsatile flow: an arteriogram. Preliminary studies are presented of the lower extremities of one healthy volunteer and four patients (one each with occlusive disease, soft-tissue tumor, arteriovenous malformation, and venous femoral-popliteal graft). Patient data are compared with accompanying conventional arteriograms, and the new method is discussed. 相似文献
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