bims-nucpor 2024-07-07 papers

Issue of 2024–07–07
three papers selected by
Sara Mingu, Johannes Gutenberg University

Commun Biol. 2024 Jun 29. 7(1): 783

Nucleoporin Elys attaches peripheral chromatin to the nuclear pores in interphase nuclei.

Semen A Doronin, Artem A Ilyin, Anna D Kononkova, Mikhail A Solovyev, Oxana M Olenkina, Valentina V Nenasheva, Elena A Mikhaleva, Sergey A Lavrov, Anna Y Ivannikova, Ruslan A Simonov, Anna A Fedotova, Ekaterina E Khrameeva, Sergey V Ulianov, Sergey V Razin, Yuri Y Shevelyov.

Transport of macromolecules through the nuclear envelope (NE) is mediated by nuclear pore complexes (NPCs) consisting of nucleoporins (Nups). Elys/Mel-28 is the Nup that binds and connects the decondensing chromatin with the reassembled NPCs at the end of mitosis. Whether Elys links chromatin with the NE during interphase is unknown. Here, using DamID-seq, we identified Elys binding sites in Drosophila late embryos and divided them into those associated with nucleoplasmic or with NPC-linked Elys. These Elys binding sites are located within active or inactive chromatin, respectively. Strikingly, Elys knockdown in S2 cells results in peripheral chromatin displacement from the NE, in decondensation of NE-attached chromatin, and in derepression of genes within. It also leads to slightly more compact active chromatin regions. Our findings indicate that NPC-linked Elys, together with the nuclear lamina, anchors peripheral chromatin to the NE, whereas nucleoplasmic Elys decompacts active chromatin.

DOI: https://doi.org/10.1038/s42003-024-06495-w

bioRxiv. 2024 Jun 17. pii: 2024.06.17.599319. [Epub ahead of print]

The DNA Damage Checkpoint Targets the Kinetochore for Relocation of Collapsed Forks to the Periphery.

Tyler Maclay, Jenna Whalen, Matthew Johnson, Catherine H Freudenreich.

Hairpin forming expanded CAG/CTG repeats pose significant challenges to DNA replication which can lead to replication fork collapse. Long CAG/CTG repeat tracts relocate to the nuclear pore complex to maintain their integrity. Forks impeded by DNA structures are known to activate the DNA damage checkpoint, thus we asked whether checkpoint proteins play a role in relocation of collapsed forks to the nuclear periphery in S. cerevisiae . We show that relocation of a (CAG/CTG) 130 tract is dependent on activation of the Mrc1/Rad53 replication checkpoint. Further, checkpoint-mediated phosphorylation of the kinetochore protein Cep3 is required for relocation, implicating detachment of the centromere from the spindle pole body. Activation of this pathway leads to DNA damage-induced microtubule recruitment to the repeat. These data suggest a role for the DNA replication checkpoint in facilitating movement of collapsed replication forks to the nuclear periphery by centromere release and microtubule-directed motion.
Highlights: The DNA damage checkpoint is needed for relocation of a structure-forming CAG repeat tract to the nuclear pore complexThe importance of Mrc1 (hClaspin) implicates fork uncoupling as the initial checkpoint signalPhosphorylation of the Cep3 kinetochore protein by Dun1 kinase modulates centromere release, which is critical for collapsed fork repositioningDamage-inducible nuclear microtubules colocalize with the CAG repeat locus and are required for relocalizationEstablishes a new role for the DNA replication and DNA damage checkpoint response to trigger repositioning of collapsed forks within the nucleus.

DOI: https://doi.org/10.1101/2024.06.17.599319

bioRxiv. 2024 Jun 22. pii: 2024.06.21.597078. [Epub ahead of print]

Coaching ribosome biogenesis from the nuclear periphery.

Yinyin Zhuang, Xiangfu Guo, Olga V Razorenova, Christopher E Miles, Wenting Zhao, Xiaoyu Shi.

Severe invagination of the nuclear envelope is a hallmark of cancers, aging, neurodegeneration, and infections. However, the outcomes of nuclear invagination remain unclear. This work identified a new function of nuclear invagination: regulating ribosome biogenesis. With expansion microscopy, we observed frequent physical contact between nuclear invaginations and nucleoli. Surprisingly, the higher the invagination curvature, the more ribosomal RNA and pre-ribosomes are made in the contacted nucleolus. By growing cells on nanopillars that generate nuclear invaginations with desired curvatures, we can increase and decrease ribosome biogenesis. Based on this causation, we repressed the ribosome levels in breast cancer and progeria cells by growing cells on low-curvature nanopillars, indicating that overactivated ribosome biogenesis can be rescued by reshaping nuclei. Mechanistically, high-curvature nuclear invaginations reduce heterochromatin and enrich nuclear pore complexes, which promote ribosome biogenesis. We anticipate that our findings will serve as a foundation for further studies on nuclear deformation.
Highlights: Nuclear invaginations regulate ribosome biogenesis by physically contacting nucleoli.High-curvature nuclear tunnels increase ribosome biogenesis.Nanopillars reduce ribosome biogenesis by transforming high-curvature nuclear invaginations to low-curvature ones.

DOI: https://doi.org/10.1101/2024.06.21.597078