Biomedical subjects

Nancy Laterreur

Publications and source records attributed to Nancy Laterreur.

3 recordsLinked to original sources

PubMed2026

Genome-wide CRISPR screens map synthetic lethal interactions across recurrent cancer driver alterations.

Synthetic lethality (SL) provides a treatment paradigm for targeting cancer with alterations in driver genes that are not conventionally druggable, including tumor suppressor genes. We execute a series of genome-wide CRISPR screens using functionally validated isogenic cell lines and conduct a large-scale SL analysis using data from the cancer dependency map (DepMap). We chart SL interactions across 15 driver alterations: FBXW7, CCNE1, CDK12, ARID1A, KMT2D, DNMT3A, TET2, KEAP1, STK11, IDH1, SF3B1, SRSF2, U2AF1, chromosome 18q loss, and chromosome 13q loss. We show validation of several SL interactions, including ARID1A and the hexosamine biosynthetic pathway aminotransferase GFPT1, STK11 with CAMK protein kinase MARK2, FBXW7 and the CDK1 regulatory kinase PKMYT1, and CCNE1 amplification and the anaphase-promoting complex or cyclosome (APC/C). In summary, this study offers a rich resource of genetic interactions across cancer drivers enabling the discovery of biological insights and drug targets for future therapeutic development.

CP: cancer↗

PubMed2006

RNase III-dependent regulation of yeast telomerase.

In bakers' yeast, in vivo telomerase activity requires a ribonucleoprotein (RNP) complex with at least four associated proteins (Est2p, Est1p, Est3p, and Cdc13p) and one RNA species (Tlc1). The function of telomerase in maintaining chromosome ends, called telomeres, is tightly regulated and linked to the cell cycle. However, the mechanisms that regulate the expression of individual components of telomerase are poorly understood. Here we report that yeast RNase III (Rnt1p), a double-stranded RNA-specific endoribonuclease, regulates the expression of telomerase subunits and is required for maintaining normal telomere length. Deletion or inactivation of RNT1 induced the expression of Est1, Est2, Est3, and Tlc1 RNAs and increased telomerase activity, leading to elongation of telomeric repeat tracts. In silico analysis of the different RNAs coding for the telomerase subunits revealed a canonical Rnt1p cleavage site near the 3' end of Est1 mRNA. This predicted structure was cleaved by Rnt1p and its disruption abolished cleavage in vitro. Mutation of the Rnt1p cleavage signal in vivo impaired the cell cycle-dependent degradation of Est1 mRNA without affecting its steady-state level. These results reveal a new mechanism that influences telomeres length by controlling the expression of the telomerase subunits.

3' Untranslated Regions↗

PubMed2006

Assessing telomeric phenotypes.

The concept of telomeres as being the end-part of eukaryotic chromosomes was first described by H. J. Muller and B. McClintock. Their pioneering work opened the path for multiple new researches and assays on a thrilling subject, with implications for various domains such as aging, replication, immortality, and cancer. Yeast has been a model of choice to study telomere length, senescence, telomerase activity, telomere cloning, and sequencing with important new techniques being discovered in this species and adapted afterward for other organisms. The main functions of telomeres include the protection of the genome from deletions, recombination, and degradation, and they are therefore essential for genome stability. Their maintenance is assured by a specific enzyme (telomerase) and it is of vital interest for the organism to maintain their length and specific structure. Multiple assays have been described to analyze telomere length and for yeast, Southern blot analysis of terminal restriction fragments (TRFs) remains one of the most popular ones to get a global picture of the state of telomeres in a given experimental setting. However, growth phenotypes (senescence) and fine-structure analyses of the chromosome terminal DNA are also becoming increasingly important.

Base Sequence↗