Viruses that infect bacteria (bacteriophages) are everywhere life is found. These deadly molecular machines inject DNA into their bacterial hosts, instructing them to make more bacteriophages. As a defense, bacteria evolved "molecular scissors"– enzymes that can snip invading DNA and stop the infection. The authors have now determined the pathways by which some bacteriophages fight back to evade their hosts' defenses. Their work shows that enzymes encoded by bacteriophages catalyze the attachment of amino acids and other molecules to DNA. These modifications act as a shield against the molecular scissors making the DNA resistant to cleavage. Since amino acids normally function in proteins, this result is surprising and suggests a chemical diversity of modifications on A,G,C and T that awaits further exploration. The bacteriophage DNA modifying enzymes discovered in this study might one day be harnessed to anchor DNA on chips, label DNA with fluorescent dyes and much more.
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.
RPB6, a common subunit shared by all three eukaryotic RNA polymerases (RNAPI, RNAPII, and RNAPIII) contains a short N-terminal tail (NTT) of so far unknown function. Here, we have revealed that NTT interacts with the PH domain (PH-D) of the p62 subunit of the general transcription/repair factor TFIIH, and solved structures of RPB6 in its free and complexed forms with PH-D by NMR. Using available cryo-EM structures, the authors have modelled the activated elongation complex of RNAPII bound to TFIIH. In addition, the authors provide evidence that the p62-RPB6 interaction plays multiple roles in transcription, transcription-coupled nucleotide excision repair, and cell proliferation, suggesting that TFIIH is engaged in all RNA polymerase systems.
Recent years have seen considerable progress in understanding the most important regulatory decision in DNA double strand break (DSB) – the transition to 5’ resection – which commits a DSB to repair via homologous recombination. Most approaches to study DSB resection begin to monitor resection 100s of bp from the DSB end. This represents a significant experimental gap, since all modern models of resection invoke critical actions of Mre11 and other proteins within the first hundred base pairs of the DSB end. The authors of this paper addressed this gap by developing a novel method with low background for high throughput sequencing of single molecules undergoing DSB resection in yeast. They were able to observe critical resection events as they happened in vivo, leading to substantive mechanistic insights such as the distance from the DSB end where Mre11 makes a key incision, which nucleases extend this nick most efficiently, and the speed with which various processing events occur ...
