UMR3348 – Stress génotoxique et cancer

Publications de l’unité

Année de publication : 2018

Anissia Ait Saada, Sarah A E Lambert, Antony M Carr (2018 Sep 18)

Preserving replication fork integrity and competence via the homologous recombination pathway.

DNA repair : DOI : S1568-7864(18)30182-4 En savoir plus

Flaws in the DNA replication process have emerged as a leading driver of genome instability in human diseases. Alteration to replication fork progression is a defining feature of replication stress and the consequent failure to maintain fork integrity and complete genome duplication within a single round of S-phase compromises genetic integrity. This includes increased mutation rates, small and large scale genomic rearrangement and deleterious consequences for the subsequent mitosis that result in the transmission of additional DNA damage to the daughter cells. Therefore, preserving fork integrity and replication competence is an important aspect of how cells respond to replication stress and avoid genetic change. Homologous recombination is a pivotal pathway in the maintenance of genome integrity in the face of replication stress. Here we review our recent understanding of the mechanisms by which homologous recombination acts to protect, restart and repair replication forks. We discuss the dynamics of these genetically distinct functions and their contribution to faithful mitoticsegregation.

Wang X, Allen WE, Wright MA, Sylwestrak EL, Samusik N, Vesuna S, Evans K, Liu C, Ramakrishnan C, Liu J, Nolan GP*, Bava FA*, Deisseroth K*. *co-last, co-corresponding author (2018 Jun 23)

Three-dimensional intact-tissue sequencing of single-cell transcriptional states.

Science (New York, N.Y.) : DOI : eaat5691 En savoir plus

Retrieving high-content gene-expression information while retaining 3D positional anatomy at cellular resolution has been difficult, limiting integrative understanding of structure and function in complex biological tissues. Here we develop and apply a technology for 3D intact-tissue RNA sequencing, termed STARmap (Spatially-resolved Transcript Amplicon Readout Mapping), which integrates hydrogel-tissue chemistry, targeted signal amplification, and in situ sequencing. The capabilities of STARmap were tested by mapping 160 to 1,020 genes simultaneously in sections of mouse brain at single-cell resolution with high efficiency, accuracy and reproducibility. Moving to thick tissue blocks, we observed a molecularly-defined gradient distribution of excitatory-neuron subtypes across cubic millimeter-scale volumes (>30,000 cells), and discovered a short-range 3D self-clustering in many inhibitory-neuron subtypes that could be identified and described with 3D STARmap.

Maria M Magiera, Puja Singh, Carsten Janke (2018 Jun 2)

SnapShot: Functions of Tubulin Posttranslational Modifications.

Cell : 1552-1552.e1 : DOI : S0092-8674(18)30644-5 En savoir plus

Post-translational modification of tubulin offers a mechanism for functional diversification of microtubules and regulation in a variety of physiological contexts. This SnapShot recaps the current state of understanding of tubulin posttranslational modifications and their functions in the regulation of biological processes. To view this SnapShot, open or download the PDF.

Maria M Magiera, Puja Singh, Sudarshan Gadadhar, Carsten Janke (2018 Jun 2)

Tubulin Posttranslational Modifications and Emerging Links to Human Disease.

Cell : 1323-1327 : DOI : S0092-8674(18)30595-6 En savoir plus

Tubulin posttranslational modifications are currently emerging as important regulators of the microtubule cytoskeleton and thus have a strong potential to be implicated in a number of disorders. Here, we review the latest advances in understanding the physiological roles of tubulin modifications and their links to a variety of pathologies.