It is shameful that half the country’s population continues to be overlooked by the international community.

A biweekly scientific journal publishing high-quality research in molecular biology and genetics, cancer biology, biochemistry, and related fields

Purines can act as endogenous molecular glues in human cells by anchoring a rate-limiting enzyme in purine biosynthesis to its inhibitor, and modifying this mechanism could provide a way to improve th...

We’ve documented more than 100 instances of apparent data manipulation in Thermo’s catalog

Douglas et al. study the E3 ligase HOIL-1, mutated in patients with a type of myopathy. Mutant HOIL-1 influences the sensitivity to disulfidptosis initiated by ZAKα–ATF4 in glucose starvation and inte...

Critical Thinking AI for constructive criticism and science evaluation

The E3-ome defines the human repertoire of ubiquitin E3 ligases, creating a unified resource that maps their diversity across the ubiquitin and ubiquitin-like systems. By consolidating fragmented knowledge, this framework provides a foundation for studying ubiquitin signaling and accelerating discovery.

Initial results from scanning through Excel files belonging to 600 published scientific papers.

DNA repair genes are generally considered tumor suppressors, as they maintain genomic stability. Here, the authors show that the exonuclease EXO1 is overexpressed in a significant proportion of tumors...

PCNA–PAF15 has a key role in determining replisome dynamics during genome replication and protecting against genome instability.

Cell Death & Disease - Targeting the FNIP2-SERCA2b axis improves metabolic and mitochondrial defects in Ataxia Telangiectasia

IMPRS-LM stands for International Max Planck Research School for Living Matter. We are interested in the molecular, chemical and physical properties

DNA-protein cross-links (DPCs) are highly toxic DNA lesions that block replication and transcription, but their impact on organismal physiology is unclear. We identified a role for the metalloprotease...

Study reveals role of “fine-grained” ancestry in predicting response to painkillers, statins, and other drugs

Mexican food scientist Raquel Gómez-Pliego works to improve the nutritional value of foods through microbial fermentation.

Small molecules toggling the ubiquitin-proteasome system (UPS) are powerful regulators of protein degradation. Yet, mechanistic knowledge of how endogenous ligands gate UPS decisions remains rudimentary. Here, we define control of UPS access to Tryptophan-2,3-dioxygenase (TDO2), which converts the essential amino acid tryptophan (Trp) to N-formylkynurenine. When Trp concentrations are limiting, TDO2 is degraded to avert tryptophanemia. Using CRISPRi screening and biochemistry, we identify a CK2-FBXW11 kinase-E3 ligase cascade that generates and recognizes tandem TDO2 phosphodegrons when not protected by Trp. Trp binding to an exosite safeguards TDO2 from phosphorylation-dependent ubiquitylation. Effects of Trp analogs on CK2-FBXW11-dependent ubiquitylation indicated that the indole, amino, and carboxylate groups are necessary for substrate shielding. Cryo-EM reveals how these moieties order a region proximal to the phosphodegrons; without Trp, this segment is flexible, enabling phosphorylation-coupled ubiquitylation. Overall, our data uncovered an endogenous small molecule allosterically stabilizing its own metabolizing enzyme through protection from a phosphorylation-ubiquitylation cascade. ### Competing Interest Statement B.A.S. is a member of the scientific advisory boards of Proxygen and Lyterian. The other authors declare no competing interests. Max Planck Society, https://ror.org/01hhn8329 European Union, ERC AdvG, UPSmeetMet, 101098161 to BAS Boehringer Ingelheim Fonds, https://ror.org/00dkye506

“I came back with a recalibrated sense of how I want to live and work,” this professor writes

DNA secondary structures, such as hairpins, cruciforms, triplexes, G-quadruplexes and iMotifs, are common, dynamic features that replication forks rou…

Pathogenic BRCA2 truncating variants in heterozygosis drive distinct cancer-linked mechanisms. Here the authors show that one causes PARPi sensitivity and HR loss via haploinsufficiency, while another...

Rogan exposes millions to climate denial. Let’s break down his tactics. 

Homologous recombination (HR) deficiency upon Breast Cancer Gene 2 (BRCA2) loss arises from defects in the formation of RAD51 nucleoprotein filaments. We demonstrate that loss of the anti-recombinase ...

Proteins traditionally confined to a single cellular compartment are increasingly recognized to exert non-canonical functions in alternative domains. The DNA methyltransferase 1 (DNMT1), classically d...

Mutations in the ATRX chromatin remodeller predispose to a developmental genetic disorder and cancer, but how it safeguards genome and telomere stability remains unresolved. Here, we uncover critical ...