The ABCD (for AntiBodies Chemically Defined) database is a repository of sequenced antibodies, integrating curated information about the antibody and its antigen with cross-links to standardized databases of chemical and protein entities. It is freely available to the academic community, accessible through the ExPASy server (https://web.expasy.org/abcd/). The ABCD database aims at helping to improve reproducibility in academic research by providing a unique, unambiguous identifier associated to each antibody sequence. It also allows to determine rapidly if a sequenced antibody is available for a given antigen.
NAR’s Breakthrough Articles present high-impact studies answering long-standing questions in the field of nucleic acids research and/or opening up new areas and mechanistic hypotheses for investigation. These articles are chosen by the Editors on the recommendation of Editorial Board Members and Referees. Articles are accompanied by a brief synopsis explaining the findings of the paper and where they fit in the broader context of nucleic acids research. They represent the very best papers published at NAR.
DNA double strand breaks (DSBs) need to be rapidly repaired to avoid cell death and genomic instability. Efficient repair of DSBs relies on a complex signalling cascade coupled with the local remodelling of chromatin and the recruitment of repair effector mechanisms. At the heart of DNA damage signalling lie the phosphatidylinositol-3-kinase-like kinase (PIKK) family, DNA-dependent protein kinase (DNA-PK), ataxia telangiectasia-mutated (ATM), and ataxia telangiectasia-mutated related (ATR). ATR and ATM respond primarily to replication fork arrest and S phase DSBs, while DNA-PK is best known for its role in promoting non-homologous end joining. Lu et al. show that the catalytic activity of DNA-PK, which reaches DSBs more quickly than the other PIKKs, is responsible for phosphorylating the histone H2AX and chromatin remodeller KAP1 and, in turn, these DNA-PK-dependent phosphorylations promote very early chromatin relaxation around the break and recruitment of repair proteins.
The maintenance of telomere length is critical to longevity and survival. The failure to properly replicate, resect, and/or form appropriate telomeric structures drives telomere shortening and genomic instability. The endonuclease CtIP is a DNA repair protein that is well-known to promote genome stability through the resection of endogenous DNA double-stranded breaks. Here, the authors show that in the absence of CtIP, human telomeres shorten rapidly to non-viable lengths. This telomere dysfunction results in an accumulation of fusions, breaks, and frank telomere loss. Additionally, CtIP suppresses the generation of circular, extrachromosomal telomeric DNA. These latter structures appear to arise from arrested DNA replication forks that accumulate in the absence of CtIP. Hence, CtIP is required for faithful replication through telomeres via its roles at stalled replication tracts. These findings demonstrate a new role for CtIP as a protector of human telomere integrity.
