Catálogo de publicaciones - revistas

<jats:title>Resolving a DNA-protein cross-link</jats:title> <jats:p> Topoisomerase 2 (TOP2) creates DNA double-strand breaks to regulate DNA topology and is critical for processes such as replication and transcription. A covalent complex between TOP2 and DNA (TOP2cc) is an intermediate in the reaction that can be trapped by drugs. Schellenberg <jats:italic>et al.</jats:italic> show how the SUMO ligase ZATT promotes the resolution of TOP2cc by means of tyrosyl-DNA phosphoesterase 2 (TDP2), both by enhancing recruitment of TDP2 to SUMOylated TOP2 and by enhancing the hydrolase activity of TDP2. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6358" page="1412" related-article-type="in-this-issue" vol="357" xlink:href="10.1126/science.aam6468">1412</jats:related-article> </jats:p>

<jats:title> Two-step role for mutant <jats:italic>TERT</jats:italic> promoters </jats:title> <jats:p> Telomeres preserve genomic stability by preventing chromosomal fusions. The recent discovery that human tumors harbor mutations in the promoter region of the telomerase gene ( <jats:italic>TERT</jats:italic> ) produced a flurry of research aimed at elucidating the role of these mutations in cancer development. Chiba <jats:italic>et al.</jats:italic> present data that reconcile many of the conflicting results reported to date (see the Perspective by Shay). In human melanoma samples and a fibroblast model, <jats:italic>TERT</jats:italic> promoter mutations acted in two steps. First, the mutations allowed cells to proliferate with short telomeres. This fueled genomic instability and up-regulation of telomerase expression, leading to uncontrolled cell proliferation. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6358" page="1416" related-article-type="in-this-issue" vol="357" xlink:href="10.1126/science.aao0535">1416</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6358" page="1358" related-article-type="in-this-issue" vol="357" xlink:href="10.1126/science.aao6963">1358</jats:related-article> </jats:p>

<jats:title>Flexible association comes at a price</jats:title> <jats:p> The CRISPR-Cas9 genome editing system is guided to its target DNA sequence by a small RNA that must search the genome to find its target site. To allow the guide RNA to bind, Cas9 must unwind the DNA at each location that it searches. Jones <jats:italic>et al.</jats:italic> used single-molecule fluorescence methods and bulk biochemistry to show that Cas9 takes 6 hours to find its target sequence, with each potential target bound for less than 30 ms. Overall, the CRISPR-Cas9 system pays for its flexible association mechanism with slow kinetics, but this can be overcome by using high concentrations of Cas9 and guide RNA. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6358" page="1420" related-article-type="in-this-issue" vol="357" xlink:href="10.1126/science.aah7084">1420</jats:related-article> </jats:p>

<jats:p>A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.</jats:p>

<jats:p>Our knowledge of the role of the human microbiome in health and disease has been growing in recent years, but analysis of the microbiome—such as amplicon sequencing of the highly conserved 16S ribosomal RNA (rRNA) gene—has proved challenging. Thanks to the rapidly declining costs of next-generation sequencing, whole-genome microbial sequencing is now emerging as a viable alternative for disease research, providing a more detailed analysis of the species present in the microbiome. Together with our invited experts, we will explore how this shift is changing the way researchers are approaching microbiome analysis, and what the additional information obtained can tell us about how the health of the microbiome impacts human health and well-being.</jats:p>