Yves Pommier

TL;DR: In this article, the authors conducted a drug screen with the NCATS mechanistic drug library of 1,978 compounds in isogenic SLFN11-knockout (KO) and wild-type (WT) leukemia cell lines and found that TAK-243, a first-in-class ubiquitin activating enzyme UBA1 inhibitor in clinical development, causes preferential cytotoxicity in SLFN-11-KO cells; this effect is associated with claspin-mediated DNA replication inhibition by CHK1 independently of ATR.

TL;DR: The inhibitory mechanism of these TFO conjugates was mediated by Top1‐induced cleavage through the use of RNA interference experiments and a camptothecin‐resistant cell line, and induction of phospho‐H2AX foci supports the DNA‐damaging activity of TFO‐CPT conjugate at specific sites.

TL;DR: In this paper, the authors show that macroH2A1.2, an RS-protective histone variant enriched on the inactive X chromosome, is required for Xi integrity and female survival.

TL;DR: Results indicate that residue 740 of top2 appears critical for both DNA and drug interactions, and the Ser740→ Trp mutation alters the DNA recognition of top 2, enhances its DNA binding, and markedly affects its interactions with inhibitors.

TL;DR: It is shown that the high heterogeneity of Chk2 levels in cancer cells is primarily due to its inactivation (owing to low gene expression, alternative splicing, point mutations, copy-number alterations and premature truncation) or reduction of protein levels.