Welcome to the nucleolar Dynamic Research Team
After DNA damage is repaired, how does a cell fully recover its functions?
Our team investigates the molecular choreography that restores transcriptional activity and nuclear/nucleolar architecture.
Our Research
One of the most fascinating – and still relatively unexplored – aspects of DNA repair concerns how cells are able to fully restore their functions once DNA lesions have been removed and genomic integrity has been re-established.
DNA damage not only interferes with transcription, replication, and cell cycle progression, but can also disrupt nuclear architecture, altering chromatin domain positioning and nucleolar organization.
Our team focuses on the molecular mechanisms that allow cells to regain normal transcriptional activity after DNA repair. In particular, we study the reorganization of nucleolar structure, an essential yet poorly understood process.
Research Project
The nucleolus is a membrane-less nuclear compartment with a highly ordered internal organization, tightly linked to its main role in ribosome biogenesis. This includes the transcription of ribosomal DNA (rDNA) by RNA polymerase I (RNAP1) and the early maturation of ribosomal RNA.
This sophisticated organization can be severely disrupted by genotoxic agents or by general cellular stress. In recent years, our work has shown that following genotoxic stress such as ultraviolet (UV) irradiation, RNA polymerase I and ribosomal DNA are relocated to the nucleolar periphery. Remarkably, nucleolar architecture is only restored once all rDNA lesions – in both active and inactive regions – have been repaired.
Complete restoration of the nucleolus therefore depends not only on efficient DNA repair systems, but also on the action of key proteins. Among these, the SMN protein (Survival of Motor Neuron), which is defective in patients with spinal muscular atrophy (SMA), plays a central role. We have demonstrated that in the absence of SMN, RNA polymerase I remains trapped at the nucleolar periphery even after DNA damage repair is completed. Strikingly, SMN translocates from Cajal bodies (CBs) to the nucleolus immediately after repair, but before nucleolar structure is fully re-established.
Other proteins, such as fibrillarin (FBL), COILIN, and nuclear myosin 1 (NM1), also appear to be required for this process of reorganization.
Our objectives
Through our research, we aim to:
- Investigate the dynamic reorganization of nucleoli following genotoxic stress.
- Elucidate the mechanisms governing nucleolar homeostasis once DNA repair has been completed.
- Identify the critical factors involved in maintaining and restoring nucleolar integrity.
Discover our team
“At the heart of every scientific breakthrough lies not only rigorous research, but also the people who carry it out. I believe that great discoveries are born from harmony, trust, and the joy of working together”
Dr. Ambra Giglia Mari
Dr. Ambra Giglia-Mari is a DR1 CNRS Senior Researcher and Group Leader of the “Nu-DyRection” team (Nucleolar Dynamics after DNA Repair in Action) at the Institute of Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM) in Lyon.
Dr. Giglia-Mari has extensive expertise in DNA repair and transcription. During her PhD, she worked in Dr. A. Sarasin’s lab studying p53 mutagenesis in skin cancers from DNA repair-deficient Xeroderma Pigmentosum patients.
During her postdoctoral research in the renowned lab of Dr. Hoeijmakers, a leader in DNA repair, she focused on the basal transcription/repair factor TFIIH, discovering and characterizing its 10th subunit mutated in the Trichothiodystrophy group A syndrome. In this period, she also developed mouse models expressing fluorescently tagged DNA repair proteins and created in vivo assays using Fluorescence Recovery After Photobleaching (FRAP) to study DNA repair kinetics in post-mitotic cells and transcription dynamics in living tissues.
In 2009, she established her independent research group in France (ATIPE/CNRS), formulating the novel hypothesis that after DNA repair, cellular activities blocked by DNA damage are actively restored through proteins and molecular mechanisms yet to be fully characterized. To explore this field, she developed assays to investigate the recovery of RNA Polymerase II transcription.
More recently, her research has centered on RNA Polymerase I transcription in the nucleolus. She demonstrated that UV-induced lesions on ribosomal DNA undergo transcription-coupled nucleotide excision repair.
Significantly, DNA damage causes profound mislocalization of nucleolar proteins and DNA, and her group studies how the nucleolus regains its proper structure after repair completion. She identified critical proteins for nucleolar homeostasis, notably the Survival Motor Neuron (SMN) protein, which plays a pivotal role in nucleolar restoration post-DNA repair.
Currently, Dr. Giglia-Mari’s team is investigating SMN’s role in nucleolar dynamics and its implications for Spinal Muscular Atrophy (SMA) pathology.
This work contributes important insights into the interplay between DNA repair, transcriptional recovery, and cellular homeostasis.
Our last news
Discover our news.
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A Visit from AFM-Téléthon Donors and Volunteers
This afternoon, our laboratory had the honor of welcoming donors and volunteers from the AFM‑Téléthon. This exchange provided an opportunity to present our research, our experimental approaches, and the equipment we use daily to better understand the molecular mechanisms involved in Spinal Muscular Atrophy. Bringing together those who support research and those who conduct it…
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Visit to Ottawa
We are delighted to have met once again our collaborators Olivier Binda and Jocelyn Côté in real life and discussed many recent results and future directions for our JPND project on SMN. SMNuHomics aims to disclose new functions of the protein SMN mutated in SMA using “omics” approaches. Our program is financed by: ANR (Agence…
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The Mari team wishes you a Merry Christmas and a Happy New Year 2026
With enthusiasm and determination, we look forward to the year ahead, ready to embrace new challenges, advance our work, and pursue new discoveries together. At the end of this wonderful team Christmas dinner, we had the chance to exchange our small gifts during our annual Secret Santa.
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La Team Mari était au rendez-vous du Relais du Muscle MyoNeurALP
Devoting the week to advancing our understanding of neuromuscular diseases and developing new treatments, then running for the AFM-Téléthon over the weekend (under the rain and still with a smile) truly exemplifies dedication. You rock !!!We are incredibly proud of you. 🥰 Thanks to Jianbo, Manon, Charlène, Camille
