Publications by authors named "Pit Preckwinkel"

Long noncoding (lnc)RNAs emerge as regulators of genome stability. The nuclear-enriched abundant transcript 1 (NEAT1) is overexpressed in many tumors and is responsive to genotoxic stress. However, the mechanism that links NEAT1 to DNA damage response (DDR) is unclear.

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A parallel quadruplex derived from the Myc promoter sequence was extended by a stem-loop duplex at either its 5'- or 3'-terminus to mimic a quadruplex-duplex (Q-D) junction as a potential genomic target. High-resolution structures of the hybrids demonstrate continuous stacking of the duplex on the quadruplex core without significant perturbations. An indoloquinoline ligand carrying an aminoalkyl side chain was shown to bind the Q-D hybrids with a very high affinity in the order K ≈10  m irrespective of the duplex location at the quadruplex 3'- or 5'-end.

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Article Synopsis
  • - Various genomic DNA sequences can form G-quadruplexes with specific structures, including one with a snap-back loop and a 3'-terminal guanine, which is relevant for evaluating their stability and ligand interactions.
  • - Detailed studies using optical methods, microcalorimetry, and NMR revealed that two types of G-quadruplex structures can coexist, suggesting their stability in cellular conditions and how they bind to ligands differently.
  • - Ligand binding analysis showed that the indoloquinoline ligand has a strong affinity for one G-quadruplex structure, while its binding ability is hindered by structural restrictions in another, highlighting the complexity of interactions within these genomic sequences.
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