Biology subjects

Mauvezin, C.

Publications and source records attributed to Mauvezin, C..

3 recordsLinked to original sources

bioRxiv2024

Adaptive replication origin activation alters chromatin dynamics and stability in cancer cells

Genome duplication, critical for cell survival and identity, requires precise origin activation to ensure accurate DNA replication and chromatin structure maintenance. In colorectal cancer cells, prolonged replication stress does not hinder cell proliferation, although the mechanisms driving cancer cell adaptability remain largely unclear. Here, we demonstrate that upon recovery, cancer cells are able to activate new replication origins in distinct domains, causing persistent changes in chromatin accessibility, nuclear morphology, and replication timing, ultimately promoting chromatin instability. Chromatin accessibility, particularly in promoter regions, increased following replication stress in a subset of cells, correlating with altered gene expression and nuclear expansion. Additionally, some genes with enhanced promoter accessibility displayed sustained expression changes, further suggesting a transcriptional shift linked to stress adaptation. Our findings reveal that colorectal cancer cells recover from severe replication stress through new origin activation, a mechanism that not only maintains cell proliferation under stress but may also accelerate tumour heterogeneity. This research underscores replication origin activation as a potential therapeutic target in combating cancer cell resilience. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=176 HEIGHT=200 SRC="FIGDIR/small/626323v1_ufig1.gif" ALT="Figure 1"> View larger version (74K): org.highwire.dtl.DTLVardef@18c8779org.highwire.dtl.DTLVardef@11249f1org.highwire.dtl.DTLVardef@1b46ecaorg.highwire.dtl.DTLVardef@d5a31c_HPS_FORMAT_FIGEXP M_FIG C_FIG MAIN HIGHLIGHTSO_LIColorectal cancer cells under severe replication stress activate new replication origins upon recovery. C_LIO_LIThe firing of new origins in distinct replication domains results in long-lasting changes in chromatin accessibility, especially in promoter regions, and is associated with alterations in nuclear morphology and replication timing. C_LIO_LIIncreased chromatin accessibility in certain promoter regions correlates with prolonged gene expression changes. C_LIO_LIThe capacity of CRC cells to recover from severe replication stress fosters chromatin instability and tumour heterogeneity. C_LI

cancer biology↗

bioRxiv2022

PIQUE: An ImageJ plugin for the quantification of toroidal nuclei in biological images

The toroidal nucleus is a novel chromosomal instability (CIN) biomarker which complements the micronucleus. Understanding the specific biological stresses leading to the formation of each CIN-associated phenotype requires the evaluation of large panels of biological images collected from different genetic backgrounds and environmental conditions. However, the quantification of toroidal nuclei is currently a manual process which is unviable on a large scale. Here, we present PIQUE (Processing of Images for the QUantification of toroidal nuclEi), a tool that automates the identification of toroidal nuclei, minimizing false positives while highly agreeing with the manual quantifications. Additionally, PIQUE identifies micronuclei for a convenient comparison of both CIN biomarkers. PIQUE is an open-source ImageJ plugin with a user-friendly interface that enables a wide scientific community to easily study the novel toroidal nucleus for the analysis of CIN levels in cellular models. AvailabilityThe plugin, the user manual, and the images used for the evaluation of PIQUE are available upon request from the authors. Contactcarles.pons@irbbarcelona.org and caroline.mauvezin@ub.edu

bioinformatics↗

bioRxiv2019

Lysosomal degradation ensures accurate chromosomal segregation to prevent genomic instability

Lysosomes, as primary degradative organelles, are the end-point of different converging pathways including macroautophagy. To date, lysosome function has mainly focused on interphase cells, while their role during mitosis remains controversial. Mitosis dictates the faithful transmission of genetic material among generations, and perturbations of mitotic division lead to chromosomal instability, a hallmark of cancer. Heretofore, correct mitotic progression relies on the orchestrated degradation of mitotic factors, which was mainly attributed to ubiquitin-triggered proteasome-dependent degradation. Here, we show that mitotic transition does not only rely on proteasome-dependent degradation, as impairment of lysosomes increases mitotic timing and leads to mitotic errors, thus promoting chromosomal instability. Furthermore, we identified several putative lysosomal targets in mitotic cells. Among them, WAPL, a cohesin regulatory protein, emerged as a novel p62-interacting protein for targeted lysosomal degradation. Finally, we characterized an atypical nuclear phenotype, the toroidal nucleus, as a novel biomarker for genotoxic screenings. Our results establish lysosome-dependent degradation as an essential event to prevent genomic instability.

cell biology↗