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  • In addition to the usual dose of compelling science, our March issue features thoughtful reflections on the last 30 years from readers, as well as past and present editors. Perhaps influenced by these pieces or by our stunning cover — or maybe it is just the changing seasons — we are in an introspective mood this month.

    Editorial
  • Over the past 30 years, Nature Structural & Molecular Biology (NSMB) has covered an enormous breadth of subjects in the broad field of molecular and structural biology. Here, some of the journal’s past and present editors recount their editorial experience at NSMB and some of the more memorable papers they worked on.

    • Guy Riddihough
    • Christopher Surridge
    • Dimitrios Typas
    Feature
  • Over the past 30 years, the field of structural biology and its associated biological insights have seen amazing progress. In this Comment, I recount several milestones in the field and how we can apply lessons from the past toward an exciting future, especially as it relates to drug discovery.

    • Cheryl H. Arrowsmith
    Comment
  • First discovered more than five decades ago, protein ubiquitylation has proven to be an omnipresent post-translational modification regulating virtually every eukaryotic cellular process. With novel clinical applications and recent studies demonstrating ubiquitylation of biomolecules other than proteins, the interest in ubiquitin will not waver any time soon.

    Editorial
  • In addition to its role in proteasomal degradation, ubiquitin has multiple roles in autophagy. It can mark proteins for autophagic degradation and actively drive autophagosome formation. Recent work shows that ubiquitin can also be conjugated to phospholipids and other biomolecules.

    • Noboru Mizushima
    Comment
  • Ubiquitination is an essential process that curtails cellular levels of damaged and redundant proteins. Chemical biologists have harnessed this natural system to induce the degradation of disease-relevant proteins. We reflect here on the potential of ‘degraders’ for targeted selectivity, and discuss the role of computer-aided drug design in shaping future advances.

    • Rory Whelan
    • Cristina Mayor-Ruiz
    Comment
  • The modification of proteins with the small protein ubiquitin constitutes a Daedalian system of posttranslational modifications in every eukaryotic cell, which is often referred to as the ubiquitin code1. Here we consider the scale and complexity of the ubiquitin system in light of recent developments.

    • Bernhard C. Lechtenberg
    • David Komander
    Comment
  • Collaboration is key to modern science, with major advances using multiple complementary approaches and dependent on sophisticated infrastructure. Yet science is also highly personal, as each person carves out a reputation and career. How does this work out in reality, and how can communities be built to benefit science and scientists?

    • Martyn David Winn
    Comment
  • Here we investigate the role of epigenetics in the formation, transcription regulation, maintenance and termination of several non-canonical chromatin structures. Using two examples, we demonstrate how studying non-canonical structures may reveal underlying mechanisms with implications for disease and propose intriguing epigenetic avenues for further exploration.

    • Albert S. Agustinus
    • Yael David
    Comment
  • The concluding statement of Watson and Crick’s historic paper on the structure of DNA1 enshrines a key tenet of molecular mechanistic cell biology: “… the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material”. Function — heredity in this case — is embedded in the redundant sequence information of the two strands of DNA. Although not always expressed as blatantly, the intimate dependence of cellular function on the mechanical level of macromolecules is inspirational. The devil is in the structural detail, and the painstaking quest for the correct details and their returns in the form of reliable knowledge knows no shortcuts.

    • Andrea Musacchio
    Comment
  • As 2023 comes to an end, we take this opportunity to look back through the pages of Nature Structural & Molecular Biology and consider some of the year’s highlights.

    Editorial
  • DNA polymerase θ (POLQ) repairs mitotic DNA breaks; this requires RHINO and PLK1, averts genomic instability and may underlie effects of POLQ inhibitors in HDR-deficient cancer cells. We discuss recent work on mitotic DNA break processing and repair, the need for multiple DSB repair pathways and implications of therapeutic POLQ targeting in cancer.

    • Marcel A. T. M. van Vugt
    • Marcel Tijsterman
    Comment
  • In January 2024, Nature Structural & Molecular Biology (NSMB) will celebrate the 30th anniversary of publishing its first issue. Though initially launched as Nature Structural Biology in 1994, the journal has since expanded its scope to include all research into the molecular underpinnings of life, with the vision that the broadest insight can be gleaned through a suite of complementary approaches.

    Editorial
  • Understanding the underlying molecular mechanisms of dosage compensation and how cells equalize gene expression from the sex chromosomes has interested scientists for more than six decades. However, with so many questions still unanswered, the field continues to capture the attention of researchers.

    Editorial