1)🚨 Excited to share the first preprint from my lab at SVI as it celebrates 4 years! 🎉 This work defines local surveillance mechanisms within the nucleoli that activate the DNA damage response (DDR) when DNA damage occurs at rRNA genes (rDNA). www.biorxiv.org/content/10.1... - ThreadSky

elainesanij.bsky.social • 36 days ago

1)🚨 Excited to share the first preprint from my lab
at SVI as it celebrates 4 years! 🎉 This work defines local surveillance mechanisms within the nucleoli that activate the DNA damage response (DDR) when DNA damage occurs at rRNA genes (rDNA). https://www.biorxiv.org/content/10.1101/2025.01.20.633984v1

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elainesanij.bsky.social•36 days ago

2/ rRNA genes are transcribed by up to 150 RNA Pol I enzymes simultaneously, creating a challenge for replication machinery. The rDNA loci are hotspots for DNA damage, but the dynamics of repair in these regions are not fully understood. 🧬⚡️

elainesanij.bsky.social•36 days ago

3/ In this study, we profiled the nucleolar proteome and chromatin landscape of stalled replication sites upon rDNA damage. This allowed us to identify the early steps of nucleolar DDR and provided a valuable resource for investigating the response to replication stress at rDNA.

elainesanij.bsky.social•36 days ago

4/ We identified early changes in nucleolar-nucleoplasmic proteome localisation upon rDNA damage and uncovered replication stress signatures involving chromatin remodelling, transcription-replication conflicts, and DNA repair pathways. 🌀

elainesanij.bsky.social•36 days ago

5/ We uncovered that upon rDNA damage, nucleolar Pol II binds to intergenic rDNA sequences, generating R-loops. These R-loops recruit DDR factors, playing a pivotal role in the early response to rDNA damage and the nucleolar DDR response. 🧬✨

elainesanij.bsky.social•36 days ago

6/ Using a small CRISPR-Cas9 synthetic lethal screen with Pol I inhibitors, we uncovered a protective role for RAD54L in nucleolar DDR. Loss of RAD54L increases R-loops and rDNA damage, disrupting nucleolar structure and sensitizing cells to PARP and RNA Pol I inhibitors. 🧬🛠️

elainesanij.bsky.social•36 days ago

7/ A huge thank you to my incredible team, co-1st authors
Dr Ruofei Liu, PhD student Anthony Xuan and collaborators who made this possible. I can’t wait to see how these insights shape future research! 🙌

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