Published in Molecular cell
The kinase domain transfers phosphate from ATP to substrates. However, the Legionella effector SidJ adopts a kinase fold, yet catalyzes calmodulin (CaM)-dependent glutamylation to inactivate the SidE ubiquitin ligases. The structural and mechanistic basis in which the kinase domain catalyzes protein glutamylation is unknown. Here we present cryo-EM...
Published in Molecular cell
Hunkeler et al. present the cryo-EM structure of HUWE1, a large HECT E3 ligase that forms a modular ring-shaped assembly with flexibly attached accessory domains. The influence of mutations associated with intellectual disabilities on HUWE1 activity and substrate recognition by HUWE1 is dissected biochemically and structurally.
Published in Molecular cell
DNA polymerase ε (Polε) carries out high-fidelity leading strand synthesis owing to its exonuclease activity. Polε polymerase and exonuclease activities are balanced, because of partitioning of nascent DNA strands between catalytic sites, so that net resection occurs when synthesis is impaired. In vivo, DNA synthesis stalling activates replication ...
Published in Molecular cell
Cholesterol metabolism is tightly associated with colorectal cancer (CRC). Nevertheless, the clinical benefit of statins, the inhibitor of cholesterol biogenesis mevalonate (MVA) pathway, is inconclusive, possibly because of a lack of patient stratification criteria. Here, we describe that YAP-mediated zinc finger MYND-type containing 8 (ZMYND8) ex...
Published in Molecular cell
The Polycomb repressive complex 2 (PRC2) is an essential epigenetic regulator that deposits repressive H3K27me3. PRC2 subunits form two holocomplexes-PRC2.1 and PRC2.2-but the roles of these two PRC2 assemblies during differentiation are unclear. We employed auxin-inducible degradation to deplete PRC2.1 subunit MTF2 or PRC2.2 subunit JARID2 during ...
Published in Molecular cell
Published in Molecular cell
Splicing is a central RNA-based process commonly altered in human cancers; however, how spliceosomal components are co-opted during tumorigenesis remains poorly defined. Here we unravel the core splice factor SF3A3 at the nexus of a translation-based program that rewires splicing during malignant transformation. Upon MYC hyperactivation, SF3A3 leve...
Published in Molecular cell
The series of RNA folding events that occur during transcription can critically influence cellular RNA function. Here, we present reconstructing RNA dynamics from data (R2D2), a method to uncover details of cotranscriptional RNA folding. We model the folding of the Escherichia coli signal recognition particle (SRP) RNA and show that it requires spe...
Published in Molecular cell
Lesions on DNA uncouple DNA synthesis from the replisome, generating stretches of unreplicated single-stranded DNA (ssDNA) behind the replication fork. These ssDNA gaps need to be filled in to complete DNA duplication. Gap-filling synthesis involves either translesion DNA synthesis (TLS) or template switching (TS). Controlling these processes, ubiq...
Published in Molecular cell
Protein synthesis must be finely tuned in the developing nervous system as the final essential step of gene expression. This study investigates the architecture of ribosomes from the neocortex during neurogenesis, revealing Ebp1 as a high-occupancy 60S peptide tunnel exit (TE) factor during protein synthesis at near-atomic resolution by cryoelectro...
