OTUD5 promotes end-joining of deprotected telomeres by promoting ATM-dependent phosphorylation of KAP1.

Appropriate repair of damaged DNA and the suppression of DNA damage responses at telomeres are essential to preserve genome stability. DNA damage response (DDR) signaling consists of cascades of kinase-driven phosphorylation events, fine-tuned by proteolytic and regulatory ubiquitination. It is not fully understood how crosstalk between these two major classes of post-translational modifications impact DNA repair at deprotected telomeres.

Safety of subcutaneous immunotherapy with carbamylated allergoids based on data from a pharmacovigilance database.

Allergen immunotherapy aims to induce tolerance, which persists after its discontinuation, to targeted allergens. However, concern exists regarding the use of subcutaneous immunotherapy with whole extracts due to frequently reported events of anaphylactic reactions. In this pharmacovigilance study, the authors assessed the safety of subcutaneous immunotherapy with the monomeric allergoid Lais-in using a database of adverse reactions documented in real-world postmarketing reports from 2010 to 2020.

Resolving the subtle details of human DNA alkyltransferase lesion search and repair mechanism by single-molecule studies.

SignificanceWe directly visualize DNA translocation and lesion recognition by the O-alkylguanine DNA alkyltransferase (AGT). Our data show bidirectional movement of AGT monomers and clusters on undamaged DNA that depended on Zn occupancy of AGT. A role of cooperative AGT clusters in enhancing lesion search efficiencies by AGT has previously been proposed.

Accuracy of Emergency Department Clinical Findings for Diagnosis of Coronavirus Disease 2019.

Study Objective: We seek to describe the medical history and clinical findings of patients attending the emergency department (ED) with suspected coronavirus disease 2019 (COVID-19) and estimate the diagnostic accuracy of patients' characteristics for predicting COVID-19.

Methods: We prospectively enrolled all patients tested for severe acute respiratory syndrome coronavirus 2 by reverse-transcriptase polymerase chain reaction in our ED from March 9, 2020, to April 4, 2020. We abstracted medical history, physical examination findings, and the clinical probability of COVID-19 (low, moderate, and high) rated by emergency physicians, depending on their clinical judgment.

Shelterin and subtelomeric DNA sequences control nucleosome maintenance and genome stability.

Telomeres and the shelterin complex cap and protect the ends of chromosomes. Telomeres are flanked by the subtelomeric sequences that have also been implicated in telomere regulation, although their role is not well defined. Here, we show that, in , the telomere-associated sequences (TAS) present on most subtelomeres are hyper-recombinogenic, have metastable nucleosomes, and unusual low levels of H3K9 methylation.