Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043346 (xeroderma pigmentosum)
 2,924 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

XPD (Xeroderma pigmentosum complementation group D) is a prototypical 5' - 3' translocating DNA helicase that exhibits frequent backward steps during DNA unwinding. Here, we propose a model of DNA unwinding by XPD. With the model we explain why XPD exhibits frequent backsteps while other helicases show rare backsteps. We explain quantitatively the single-molecule data on probability of -1-bp step and mean dwell time of one step versus ATP concentration for XPD at fixed large external force applied to the ends of the DNA hairpin to unzip the hairpin. We study DNA unwinding velocity, probability of -1-bp step and mean dwell time of one step for XPD versus external force at various ATP concentrations. We compare DNA unwinding dynamics of the 5' - 3' helicase XPD with that of 3' - 5' helicase RecQ. Our results show that the DNA unwinding velocity of XPD is sensitively dependent on the external force, which is contrast to RecQ that shows insensitive dependence of DNA unwinding velocity on the external force, explaining the experimental data showing that RecQ is an "optimally active" helicase while XPD is a "partially active" helicase. The DNA unwinding dynamics of different helicases under the external force is also studied.
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PMID:Dynamics of DNA unwinding by helicases with frequent backward steps. 2902 46

Transcription preinitiation complexes (PICs) are vital assemblies whose function underlies the expression of protein-encoding genes. Cryo-EM advances have begun to uncover their structural organization. Nevertheless, functional analyses are hindered by incompletely modeled regions. Here we integrate all available cryo-EM data to build a practically complete human PIC structural model. This enables simulations that reveal the assembly's global motions, define PIC partitioning into dynamic communities and delineate how structural modules function together to remodel DNA. We identify key TFIIE-p62 interactions that link core-PIC to TFIIH. p62 rigging interlaces p34, p44 and XPD while capping the DNA-binding and ATP-binding sites of XPD. PIC kinks and locks substrate DNA, creating negative supercoiling within the Pol II cleft to facilitate promoter opening. Mapping disease mutations associated with xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome onto defined communities reveals clustering into three mechanistic classes that affect TFIIH helicase functions, protein interactions and interface dynamics.
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PMID:Transcription preinitiation complex structure and dynamics provide insight into genetic diseases. 3111 Feb 95


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