Phosphorylation-mediated conformational change regulates human SLFN11.

Human Schlafen 11 (SLFN11) is sensitizing cells to DNA damaging agents by irreversibly blocking stalled replication forks, making it a potential predictive biomarker in chemotherapy. Furthermore, SLFN11 acts as a pattern recognition receptor for single-stranded DNA (ssDNA) and functions as an antiviral restriction factor, targeting translation in a codon-usage-dependent manner through its endoribonuclease activity. However, the regulation of the various SLFN11 functions and enzymatic activities remains enigmatic.

Structural basis for human OGG1 processing 8-oxodGuo within nucleosome core particles.

Base excision repair (BER) is initialized by DNA glycosylases, which recognize and flip damaged bases out of the DNA duplex into the enzymes active site, followed by cleavage of the glycosidic bond. Recent studies have revealed that all types of DNA glycosylases repair base lesions less efficiently within nucleosomes, and their repair activity is highly depended on the lesion's location within the nucleosome. To reveal the underlying molecular mechanism of this phenomenon, we determine the 3.

Lysosomal endonuclease RNase T2 and PLD exonucleases cooperatively generate RNA ligands for TLR7 activation.

Toll-like receptor 7 (TLR7) is essential for recognition of RNA viruses and initiation of antiviral immunity. TLR7 contains two ligand-binding pockets that recognize different RNA degradation products: pocket 1 recognizes guanosine, while pocket 2 coordinates pyrimidine-rich RNA fragments. We found that the endonuclease RNase T2, along with 5' exonucleases PLD3 and PLD4, collaboratively generate the ligands for TLR7.

Energy-driven genome regulation by ATP-dependent chromatin remodellers.

The packaging of DNA into chromatin in eukaryotes regulates gene transcription, DNA replication and DNA repair. ATP-dependent chromatin remodelling enzymes (re)arrange nucleosomes at the first level of chromatin organization. Their Snf2-type motor ATPases alter histone-DNA interactions through a common DNA translocation mechanism.