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  • Journal article

  • A unique arginine cluster in PolDIP2 enhances nucleotide binding and DNA synthesis by PrimPol

    • Authors : Kash, Kazutoshi; Stojkovič, Gorazd; Ruiz, Cristina Velázquez (2020)

  • Replication forks often stall at damaged DNA. Resumption of DNA synthesis can occur by replacement of the replicative DNA polymerase with specialized, error-prone translesion DNA polymerases (TLS), that have higher tolerance for damaged substrates. Several of these polymerases (Polλ, Polη and PrimPol) are stimulated in DNA synthesis through interaction with PolDIP2, however the mechanism of this PolDIP2-dependent stimulation is still unclear. Here we show that Pri...
  • Periodicals (Báo – Tạp chí)

  • Stability of the pH-Dependent Parallel-Stranded d(CGA) Motif

    • Authors : Luteran, E. M; Kahn, J. D (2020)

  • This article addresses the stability of the d(CGA) triplet motif and variants in solution. Our study reveals changes in thermodynamic stability and nuclease resistance in response to pH. The identity of the 5′-nucleobase within each triplet and the position and frequency of different triplets within stretches of d(CGA) triplets can tune parallel-stranded duplex stability. This tunability can be used for nanotechnological applications where the specificity of ...
  • Journal article

  • Non-denaturing bisulfite treatment and single-molecule real-time sequencing reveals d-loop footprints, their length, position and distribution

    • Authors : Shah, Shanaya Shital; Hartono, Stella; Chédin, Frédéric (2020)

  • Displacement loops (D-loops) are signature intermediates formed during homologous recombination. Numerous factors regulate D-loop formation and disruption, thereby influencing crucial aspects of DNA repair, including donor choice and the possibility of a crossover outcome. While D-loop detection methods exist, it is currently unfeasible to assess the relationship between D-loop editors and D-loop characteristics such as length and position. Here, we developed a novel in...
  • Periodicals (Báo – Tạp chí)

  • The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases

    • Authors : Mäkinen, Janne J; Shin, Yeonoh (2020)

  • RNA polymerases (RNAPs) synthesize RNA from NTPs, whereas DNA polymerases synthesize DNA from 2’dNTPs. DNA polymerases select against NTPs by using steric gates to exclude the 2’ OH, but RNAPs have to employ alternative selection strategies. In single-subunit RNAPs, a conserved Tyr residue discriminates against 2’dNTPs, whereas selectivity mechanisms of multi-subunit RNAPs remain hitherto unknown. Here we show that a conserved Arg residue uses a two-pronged s...
  • Journal article

  • Direct Visualization of Translesion DNA Synthesis Polymerase IV at the Replisome

    • Authors : Tuan, Pham Minh (2023)

  • In bacterial cells, DNA damage tolerance is manifested by the action of translesion DNA polymerases that can synthesize DNA across template lesions that typically block the replicative DNA polymerase III. It has been suggested that one of these TLS DNA polymerases, DNA polymerase IV, can either act in concert with the replisome, switching places on the b sliding clamp with DNA polymerase III to bypass the template damage, or&...
  • Journal article

  • Condensed chromatin behaves like a solid on the mesoscale in vitro and in living cells

    • Authors : Strickfaden, Hilmar; Tolsma, Thomas; Sharma, Ajit (2020)

  • The association of nuclear DNA with histones to form chromatin is essential to the temporal and spatial control of eukaryotic genomes. In this study, we examined the physical state of chromatin in vitro and in vivo. Our in vitro studies demonstrate that MgCl2-dependent self-association of native chromatin fragments or reconstituted nucleosomal arrays produced supramolecular condensates whose constituents are physically constrained and solid-like. Liquid chromatin conde...
  • Journal article

  • High resolution studies of DNA lesion bypass by human DNA polymerase δ holoenzymes

    • Authors : Dannenberg, Rachel L. (2023)

  • During DNA replication, DNA lesions present in lagging strand templates are initially encountered by DNA polymerase  (pol ). The historical view for what transpires from these encounters is that replication of the afflicted lagging strand template abruptly stops, activating DNA damage tolerance (DDT) pathways that replicate the offending lesion and adjacent DNA sequence, allowing pol  to resume downstream. However, qualitative studies observed that human p...
  • Journal article

  • Decoding the Dual Recognition Mechanism of Glucocorticoid Receptor for DNA and RNA: Sequence vs. Shape

    • Authors : Johanna, Hörberg (2023)

  • Transcription factors (TFs) regulate eukaryotic transcription through selecting DNA-binding, can also specifically interact with RNA, which may present another layer of transcriptional control. The mechanisms of the TFs-DNA recognition are often well-characterised, while the details of TFs-RNA complexation are less understood. Here we investigate the dual recognition mechanism of the glucocorticoid receptor (GR), which interacts with similar affinities with consen...
  • Journal article

  • Structural analysis of SALL4 zinc-finger domain reveals a link between AT-rich DNA binding and Okihiro syndrome

    • Authors : Watson, James A. (2023)

  • Spalt-like 4 (SALL4) maintains vertebrate embryonic stem cell identity and is required for the development of multiple organs, including limbs. Mutations in SALL4 are associated with Okihiro syndrome and SALL4 is also a known target of thalidomide. SALL4 protein has a distinct preference for AT-rich sequences, recognised by a pair of zinc fingers at the C-terminus. However, unlike many characterised zinc finger proteins, SALL4 shows flexibl...