Cells.: co-auth.: group B.Thorens

Cells. 2022 May 25;11(11):1737. doi: 10.3390/cells11111737.

Homocysteine Metabolism Pathway Is Involved in the Control of Glucose Homeostasis: A Cystathionine Beta Synthase Deficiency Study in Mouse

Céline Cruciani-Guglielmacci 1Kelly Meneyrol 1Jessica Denom 1Nadim Kassis 1Latif Rachdi 2Fatna Makaci 2Stéphanie Migrenne-Li 1Fabrice Daubigney 1Eleni Georgiadou 3Raphaël G Denis 1 2Ana Rodriguez Sanchez-Archidona 4Jean-Louis Paul 5Bernard Thorens 4Guy A Rutter 3 6 7Christophe Magnan 1Hervé Le Stunff 8Nathalie Janel 1


Cystathionine beta synthase (CBS) catalyzes the first step of the transsulfuration pathway from homocysteine to cystathionine, and its deficiency leads to hyperhomocysteinemia (HHcy) in humans and rodents. To date, scarce information is available about the HHcy effect on insulin secretion, and the link between CBS activity and the setting of type 2 diabetes is still unknown. We aimed to decipher the consequences of an inborn defect in CBS on glucose homeostasis in mice. We used a mouse model heterozygous for CBS (CBS+/-) that presented a mild HHcy. Other groups were supplemented with methionine in drinking water to increase the mild to intermediate HHcy, and were submitted to a high-fat diet (HFD). We measured the food intake, body weight gain, body composition, glucose homeostasis, plasma homocysteine level, and CBS activity. We evidenced a defect in the stimulated insulin secretion in CBS+/- mice with mild and intermediate HHcy, while mice with intermediate HHcy under HFD presented an improvement in insulin sensitivity that compensated for the decreased insulin secretion and permitted them to maintain a glucose tolerance similar to the CBS+/+ mice. Islets isolated from CBS+/- mice maintained their ability to respond to the elevated glucose levels, and we showed that a lower parasympathetic tone could, at least in part, be responsible for the insulin secretion defect. Our results emphasize the important role of Hcy metabolic enzymes in insulin secretion and overall glucose homeostasis.

Keywords: autonomic nervous system; hyperhomocysteinemia; insulin secretion; type 2 diabetes.

Life Sci Alliance.: auth.: group van Leeuwen

Life Sci Alliance. 2022 Jan 11;5(4):e202101153. doi: 10.26508/lsa.202101153. Print 2022 Apr.

Chl1 helicase controls replication fork progression by regulating dNTP pools

Amandine Batté 1Sophie C van der Horst 1Mireille Tittel-Elmer 1 2Su Ming Sun 1Sushma Sharma 3Jolanda van Leeuwen 4Andrei Chabes 3Haico van Attikum 5


Eukaryotic cells have evolved a replication stress response that helps to overcome stalled/collapsed replication forks and ensure proper DNA replication. The replication checkpoint protein Mrc1 plays important roles in these processes, although its functional interactions are not fully understood. Here, we show that MRC1 negatively interacts with CHL1, which encodes the helicase protein Chl1, suggesting distinct roles for these factors during the replication stress response. Indeed, whereas Mrc1 is known to facilitate the restart of stalled replication forks, we uncovered that Chl1 controls replication fork rate under replication stress conditions. Chl1 loss leads to increased RNR1 gene expression and dNTP levels at the onset of S phase likely without activating the DNA damage response. This in turn impairs the formation of RPA-coated ssDNA and subsequent checkpoint activation. Thus, the Chl1 helicase affects RPA-dependent checkpoint activation in response to replication fork arrest by ensuring proper intracellular dNTP levels, thereby controlling replication fork progression under replication stress conditions.

I. Lopez-Mejia and N. Vastenhouw were in “L’Actu” magazine regarding their FBM interdisciplinary Grant, Dec. 2021

Among the 4 interdisciplinary projects selected by the Faculty of Biology and Medicine to get fundings, 2 were proposed by members of the CIG:

List of all awardees on the UNIL web magazine: https://news.unil.ch/display/1638977433273

Congratulations to several Genopode (ex-)members on their participation in the Vortex race of 3km run!

On 43 teams running the Vortex race last Nov. 25th, the Génopode’s ones arrived 11th and 24th

Congratulation to the participants!

11th: Team les mardistes composed of Carlos L., Manuel B. and Gérard B.
24th: Team Jeyaly composed of Yann E., Lyam B. and Jean-Yves R.

All results can be found here: https://4bd5409b-b6db-46f8-b130-1f5610ea87d6.filesusr.com/ugd/bc83a2_e8dfd4e052fb4a07b2693932fad98ff4.pdf

Further information on the run: https://www.essul.ch/