April 12, 2022

Welcome to the April session!

We are excited to host two great talks this month:

Working less, working better: how end-joining is turned off at telomeres

Stefano Mattarocci, PhD

CEA, France

Regulation and limitations of DRC signaling upon replication stress and consequences on cell outcome

Olivier Gavet, PhD

CNRS, France

Chairs of the session will be:

About the speaker: Stefano Mattarocci

Stefano Mattarocci

Stefano Mattarocci graduated in Biological Sciences at Sapienza University of Rome. After his PhD in Genetics and Cell Biology (2009), he did two post-doc experiences: Prof. D. Shore (Geneve University) and Dr. T. Teixiera (IBPC, Paris) labs. Since 2020, he is recruited at the Dr. S. Marcand lab (CEA, Fontenay aux-Roses, Paris) as an INSERM researcher.
Stefano is interested in how telomeres, the ends of chromosomes, protect the integrity of the genome and exert a control on cell proliferation capacity.
In collaboration with N. Thomä lab (FRM, Basel), he discovered the tridimensional architecture of the budding yeast telomere structure. Then he turned his interest to study how telomeres are replicated. He discovered an unexpected function of one telomere protein (ScRif1), being able to control the overall genome replication timing. This mechanism has been then found conserved in most organisms.
Stefano moved to France in 2017 and he studied the correlation between the progressive telomere shortening and the cell proliferation capability. He set up a method (CRISPR-Cas9-based) to efficiently induce a single telomere shortening and analyzed the budding yeast cell’s fate at single-cell lineage level (paper in preparation).
He is currently studying how telomere proteins inhibit telomere-fusions, a catastrophic event for genome stability. The main aim is to dissect the mechanisms of telomere proteins controlling the activities of KU and MRX, the two key complexes promoting budding yeast end-fusions.

About the speaker: Olivier Gavet

Olivier Gavet

I did a PhD in the laboratory of Dr. A. Sobel in Paris on microtubule dynamics and the role of the MT destabilizing protein Op18/stathmin. Then, I joined the lab. of Dr M. Bornens at Institut Curie (still in Paris) for a junior post-doc to work on centriole biogenesis. I did a senior post-doc in the lab. of Jon Pines at the Gurdon Institute in Cambridge, UK to work on the regulation of the master mitotic kinase CyclinB1-Cdk1. I obtained a permanent position in France at Sorbonne Université as an associate professor. Finally, since 2015, I set up my own group at Institut Gustave Roussy (few km outside Paris) working on cell cycle regulation and genetic stability.

In human cells, ATR/Chk1 signaling couples S phase exit with expression of mitotic inducers and prevents premature mitosis upon replication stress (RS). Nonetheless, under-replicated DNA can persist at mitosis, prompting chromosomal instability. To decipher how the DNA replication checkpoint (DRC) allows cells to enter mitosis over time upon RS, we developed a FRET-based Chk1 activity sensor. During unperturbed growth, a basal Chk1 activity is sustained along S phase and relies on replication origin firing. Incremental RS triggers stepwise Chk1 over-activation delaying S-phase, suggesting a rheostat-like role of DRC coupled to the replication machinery. Upon RS, Chk1 inactivates as DNA replication terminates but surprisingly reactivates in a subset of G2 cells, which relies on Cdk1/2 and Plk1 and prevents mitotic entry. Yet, active Chk1 is overridden to drive mitosis onset, revealing checkpoint adaptation. Cell division following Chk1 reactivation in G2 results in a p53/p21-dependent G1 arrest, eliminating daughter cells from proliferation.

About GiiN webinar series

The first GiiN Webinars Series (2021-2022) happens every second Tuesday of the month. It covers latest cutting-edge research in the field of genome stability from two scientists working either in the Italian territory or abroad. This series operates under the kind patronage of AIRC Italian Foundation for Cancer Research.

For more information, to volunteer or to be added to our mailing list, contact us at genomeintegrityitaly@gmail.com