New method paper:
Bennie Lemmens et al @scilifelab.se describe 3D-SPARK, a super-resolution microscopy method that maps changes in DNA replication nanostructures in response to genetic perturbations or drugs, linking spatial cell biology with DNA synthesis dynamics
www.embopress.org/doi/full/10....
We finally reveal a strand-specific role of MajSat RNA by using forward / reverse strand-specific locked nucleic acid DNA gapmers. We found the forward MajSat RNA to be regulating the replication timing of the PCH, suggesting ncRNA as regulators of replication timing.
Loss of H3K36me3 at pericentromeric heterochromatin disrupts transcription:
↑ RNA Pol II Ser5 (initiation)
↓ RNA Pol II Ser2 (elongation)
↓ Major satellite RNA levels
Together, these changes point to transcriptional stalling and loss of MajSat RNA.
When we depleted H3K36me3 specifically from pericentromeric heterochromatin, replication timing was disrupted.
⚡ Instead of a neatly ordered sequence, PCH began replicating together with other heterochromatic regions - a loss of temporal control linked to genome instability.
To probe the role of H3K36me3 at PCH, we developed a new approach:
✨ Nanobody-mediated targeting of oncohistone H3.1 K36M directly to pericentromeric heterochromatin.
This locally reduced H3K36me3 without altering other histone modifications, and elsewhere in the chromatin.
Different perspectives on epigenetic dynamics and memory, especially before genome replication:
We show H3K36me3 is dynamically enriched at pericentromeric heterochromatin (PCH) before its replication and erased after, tightly linking epigenetics and replication timing. doi.org/10.1038/s443...
🧬⚡Your sunscreen is only half the story
We show that near-infrared light makes UV damage WORSE. nIR loosens DNA packaging, creating a repair traffic jam that increases breaks. We are ignoring the invisible majority of solar radiation that hacks DNA repair.
doi.org/10.1038/s415...
@tuda.bsky.social
Warmest congratulations to Dr. Sunil K. Pradhan (@sunil-k-pradhan.bsky.social) on successfully defending his PhD thesis on genome replication and epigenetic regulation in mammalian cells! Wishing you continued success as you embark on your next chapter. 🎓"
Could I be added? Thanks!
