A dual inhibitor of PIP5K1C and PIKfyve prevents SARS-CoV-2 entry into cells.

The SARS-CoV-2 pandemic has had an unprecedented impact on global public health and the economy. Although vaccines and antivirals have provided effective protection and treatment, the development of new small molecule-based antiviral candidates is imperative to improve clinical outcomes against SARS-CoV-2. In this study, we identified UNI418, a dual PIKfyve and PIP5K1C inhibitor, as a new chemical agent that inhibits SARS-CoV-2 entry into host cells.

TRIP13 Participates in Immediate-Early Sensing of DNA Strand Breaks and ATM Signaling Amplification through MRE11.

Thyroid hormone receptor-interacting protein 13 (TRIP13) participates in various regulatory steps related to the cell cycle, such as the mitotic spindle assembly checkpoint and meiotic recombination, possibly by interacting with members of the HORMA domain protein family. Recently, it was reported that TRIP13 could regulate the choice of the DNA repair pathway, i.e.

Ewing sarcoma protein promotes dissociation of poly(ADP-ribose) polymerase 1 from chromatin.

Poly(ADP-ribose) polymerase 1 (PARP1) facilitates DNA damage response (DDR). While the Ewing's sarcoma breakpoint region 1 (EWS) protein fused to FLI1 triggers sarcoma formation, the physiological function of EWS is largely unknown. Here, we investigate the physiological role of EWS in regulating PARP1.

SHPRH as a new player in ribosomal RNA transcription and its potential role in homeostasis of ribosomal DNA repeats.

There are hundreds of copies of rDNA repeats in mammalian chromosomes and the ratio of active, poised, or inactive rDNA is regulated in epigenetic manners. Recent studies demonstrated that a post-DNA replication repair enzyme, SHPRH affects rRNA transcription by recognizing epigenetic markers on rDNA promoters and unveiled potential links between DNA repair and ribosome biogenesis. This study suggests that SHPRH could be a link between mTOR-mediated epigenetic regulations and rRNA transcription, while concomitantly affecting genomic integrity.