Emeritus Professor Nordenskiöld, Lars
Mammalian telomeres consist of the tandemly arranged DNA sequence repeats TTAGGG that act as a platform for the recruitment of the capping structure at the end of the linear chromosomes, which protect their ends from incorrect DNA repair and degradation. In humans, this consists of the six-protein Shelterin complex as well as nucleosomes that package 5–15 kbp of telomeric DNA into chromatin. Aberrant regulation of telomeres has been linked with cancer development and ageing-associated pathologies. However, almost nothing was known about the structure of telomeric chromatin at the molecular level. Recently (Soman et al, Nature, 699, 1048, 2022; https://www.nature.com/articles/s41586-022-05236-5), we characterized telomeric chromatin fibres with EM and single-molecule magnetic tweezers. We determined the Cryo-EM structure of the condensed telomeric tetra-nucleosome chromatin fibre, which revealed a novel columnar architecture.
A general aim of the Nordenskiöld research is the unravelling of the principles and control of the packaging of DNA in the cell nucleus within the context of chromatin with emphasis to the unique telomeric chromatin. We are interested in understanding the molecular interactions and the (electrostatic) mechanisms that induce, stabilize and regulate chromatin folding and what are the implications of this for telomere maintenance and its relation to cancer and aging.
Research Areas
Telomere and chromatin structural biology, Chromatin and DNA biophysics and phase separation; Chromatin computer modelling; DNA computational biology
- Aghil Soman, Sook Yi Wong, Nikolay Korolev, Wahyu Surya, Simon Lattmann, Vinod K. Vogirala, Qinming Chen, Nikolay V. Berezhnoy, John van Noort, Daniela Rhodes, and Lars Nordenskiöld, (2022) “Columnar structure of human telomeric chromatin”, Nature, 609, 1048–1055, 2022: https://doi.org/10.1038/s41586-022-05236-5
- Sook Yi Wong, Aghil Soman, Nikolay Korolev, Wahyu Surya, Qinming Chen, John van Noort, Lars Nordenskiöld (2024), “The shelterin component TRF2 mediates the columnar stacking of human telomeric chromatin”, EMBO Journal, 43(1), 87-111: https://doi.org/10.1038/s44318-023-00002-3
- Lars Nordenskiöld, Xiangyan Shi, Nikolay Korolev, Lei Zhao, Ziwei Zhai, and Björn Lindman (2024) “Liquid-liquid phase separation (LLPS) in DNA and chromatin systems from the perspective of colloid physical chemistry”, Advances in Colloid and Interface Science, Volume 326, 103133: https://doi.org/10.1016/j.cis.2024.103133
- Tiedong Sun, Nikolay Korolev, Alexander Lyubartsev, and Lars Nordenskiöld, (2025) "Coarse-grained modeling of nucleosome arrays reveals the salt dependent chromatin fiber conformational variability", Journal of Chemical Physics, 162, 024101: https://doi.org/10.1063/5.0242509
- Nikolay Korolev, Tiedong Sun, Alexander P. Lyubartsev, Lars Nordenskiöld (2025), “Coarse-Grained Modeling of Electrostatic Interactions in Chromatin”, WIREs Computational Molecular Science, 15:e70059: https://doi.org/10.1063/5.0242509