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Online Now: FANCA-dependent FEN1 recruitment suppresses transcription-replication conflicts and PARPi sensitivity Online now:

Online Now: SenCat: Cataloging human cell senescence through multi-omic profiling of multiple senescent primary cell types Online now:

🚨 Today we report cryo-EM structures of the Bxb1 integrase complexed with its attB/attP DNA substrates before, during and after recombination. Using these structures, we engineer Bxb1 mutants with improved recombination efficiencies and altered sequence recognition properties. Check it out! ⬇️

New research out in @cp-molcell.bsky.social from Rajan Jain & Ashley Karnay (@penncvi.bsky.social) finds that transcription & cohesin direct domain boundary spatial positioning & are linked to Friedreich’s ataxia @pennepigenetics.bsky.social tinyurl.com/yc4dcvmb

In this issue of Molecular Cell, Mallory et al. use single-molecule DNA methyltransferase footprinting to provide an unprecedented view of the chromatin and transcriptional state of reporter plasmid molecules in human cells.

In this issue, Zhang and Cañari-Chumpitaz et al. find that RNA polymerase (RNAP) preferentially binds to the apices of supercoiled DNA plectonemes, which facilitates promoter escape but imposes a torsional trade-off during elongation. In the presence of torsional blocks, it generates twin supercoiling domains and drives cooperative transcription.

Soma et al. present cryo-EM structures of the large serine recombinase Bxb1 bound to attP and attB substrates and provide mechanistic insights into attP/attB recognition, synaptic complex formation, and strand exchange via subunit rotation, enabling structure-guided engineering of Bxb1 variants with reprogrammed DNA preferences and enhanced recombination activity.

Gregory J. Hannon passed away in April 2026 at the age of 61. A towering figure in modern molecular biology, Greg influenced remarkably diverse areas of science. His work reshaped our understanding of gene regulation, advanced the discovery of tumor suppressors that regulate the cell-cycle machinery, and uncovered fundamental mechanisms of RNA interference. By establishing core principles of small RNA biology, he not only transformed our mechanistic view of RNA-silencing pathways but also pioneered functional genomics approaches that revolutionized basic and biomedical research in mammalian systems.

Zhou et al. reveal how the neural pioneer factor Ascl1-E12a engages nucleosomes through distinct interactions that together drive DNA unwrapping and repositioning. These mechanisms enable chromatin opening and efficient reprogramming to a neural fate, providing insight into how pioneer transcription factors overcome nucleosomal barriers to initiate cell fate transitions.

Budinich et al. show that locally produced transcripts reinforce the nucleation of pathogenic condensates formed by mutant ENL at permissive target loci. This RNA-enhanced condensate nucleation in turn increases mutant ENL occupancy and transcriptional bursting at key oncogenic targets, thus surpassing the gene activation threshold required for tumorigenesis.

Wang et al. uncover a non-canonical role for FANCA in safeguarding genome stability during DNA replication. FANCA recruits the flap endonuclease FEN1 to lagging strands to suppress transcription-replication conflicts, a function that becomes essential under oncogene-induced replication stress, rendering tumors vulnerable to PARP inhibition despite intact homologous recombination repair.

Anerillas et al. generated SenCat, a multi-omic atlas of senescence across diverse human cell types, revealing no universal markers but conserved damage-response and metabolic pathways. Machine-learning-derived signatures robustly recognize and quantify senescence across datasets, tissues, and species, providing a broadly applicable framework for identifying senescent cells in vivo.