Reviews & Analysis

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  • Although oxidative stress has long been considered to be a major factor contributing to telomere shortening, recent work has established that oxidative stress and DNA damage are linked to telomere lengthening. Now, Opresko and colleagues resolve this apparent discrepancy by showing that differential modulation of telomerase activity depends on the origin of a common oxidative guanine lesion.

    • Jaya Sarkar
    • Yie Liu
    News & Views
  • This Perspective focuses on five distinct regulatory elements that have been recognized as being critical for generating and modulating oscillatory dynamics in time and space, in both natural and synthetic biological networks.

    • Yangxiaolu Cao
    • Allison Lopatkin
    • Lingchong You
    Perspective
  • Clock proteins are controlled by multiple post-translational modifications during the circadian cycle. In this Review, the authors examine how post-translational modifications influence the stability, interactions and activity of mammalian clock proteins and how they contribute to proper clock function or are altered in circadian disorders.

    • Arisa Hirano
    • Ying-Hui Fu
    • Louis J Ptáček
    Review Article
  • This Review examines the molecular mechanisms underlying the plant circadian clock, highlighting the functions of transcriptional circuits and post-translational regulation in timing and describing how clock components integrate and respond to environmental signals.

    • Maria A Nohales
    • Steve A Kay
    Review Article
  • During protein synthesis, the growing nascent polypeptide chain acts as a positive or negative regulator of the rate of peptide-bond formation and ribosomal fidelity, and influences the efficiency of downstream protein-folding and targeting events. At a recent international meeting held on the banks of Lake Kawaguchi in Japan, scientists and students investigating diverse aspects of nascent-chain biology met to discuss their latest findings in the scenic presence of Mount Fuji.

    • Daniel N Wilson
    • Patricia L Clark
    Meeting Report
  • A conserved long noncoding RNA expressed at the 5S rDNA ribosomal locus has acquired a novel function in alternative-splicing regulation in primates, owing to the insertion of a mobile Alu element. This discovery opens new perspectives regarding the roles of transposable elements in expanding the human transcriptome and may be applied as a biotechnology tool to drive gene-specific changes in alternative splicing.

    • Reini F Luco
    News & Views
  • Drosophila Skywalker regulates the GTPase Rab35, thereby controlling the turnover of synaptic-vesicle proteins. A new crystal structure of the TBC domain of Skywalker reveals an unexpected phosphoinositide-binding pocket, which is critical for synaptic function and is disrupted in DOORS syndrome–causing mutations in the human Skywalker homolog TBC1D24.

    • Steven J Del Signore
    • Avital A Rodal
    News & Views
  • The degradation of mRNAs involves removal of the 5′ protective cap via a decapping-enzyme complex, in a largely irreversible process that commits the transcript for destruction. Understanding how the decapping reaction is catalyzed and regulated are major goals in the field. New data suggest how the chemistry of decapping is controlled and orchestrated within the cell.

    • Jeff Coller
    News & Views
  • Methicillin resistance in the clinically important bacterium Staphylococcus aureus (MRSA) has evolved in multiple S. aureus lineages through acquisition of chromosomally integrating mobile genetic elements named SCCmec. Now Rice and colleagues show that the conserved SCCmec cch gene encodes an active DNA helicase, thus suggesting that extrachromosomal replication is part of the enigmatic SCCmec horizontal-transfer mechanism.

    • Joshua P Ramsay
    News & Views
  • A potent toxin present in the venom of a fish-hunting cone snail is a minimized insulin (Con-Ins G1) lacking key residues involved in the receptor binding of most insulins. New data show that Con-Ins G1 nevertheless binds potently to the human insulin receptor, owing to a rearrangement that compensates for the lack of a critical binding residue.

    • Pierre De Meyts
    News & Views
  • Cells deploy the Hsp100 family of ATP-dependent machines to work with cellular chaperones in dismantling dangerous protein aggregates. New studies reveal an unprecedented spiral structure that provides mechanistic insight into the protein disaggregase Hsp104.

    • Steven E Glynn
    • Peter Chien
    News & Views
  • Bacteria and phages are engaged in a molecular arms race, constantly coevolving to best each other. The crystal structure of the anti-CRISPR protein AcrF3 bound to Cas3, an essential component of CRISPR-based immunity, sheds light on how phages have found ways to suppress bacterial immunity.

    • John Mallon
    • Scott Bailey
    News & Views
  • In this Review, the authors discuss recent advances in understanding how post-translational modifications of the RNA polymerase II C-terminal domain (CTD) regulate transcription and RNA processing events and control gene expression.

    • Justyna Zaborowska
    • Sylvain Egloff
    • Shona Murphy
    Review Article
  • Mutations in the BRCA1 and BRCA2 genes strongly predispose carriers to breast and ovarian cancers. Two new studies reveal that FANCD2, a key component of the Fanconi anemia pathway, is essential for the survival of cells with BRCA1 or BRCA2 mutations. These findings pave the way for new 'synthetic lethal' strategies to kill BRCA-mutated cancers.

    • Christophe Lachaud
    • John Rouse
    News & Views
  • Ribosome profiling provides a snapshot of the mRNA positions of all elongating ribosomes in the cell. A new powerful enhancement of the technique, translation complex profile sequencing (TCP–seq), extends this mapping to scanning ribosomal complexes. In addition to its usefulness as a tool for studying the regulation of translation initiation, TCP–seq provides specific and powerful signatures of bona fide translation.

    • Pavel V Baranov
    • Gary Loughran
    News & Views
  • Unrestrained 53BP1 activity causes fusions of dysfunctional telomeres and embryonic lethality associated with misrepair of DNA double-strand breaks in BRCA1-deficient mice. However, the physiological role of 53BP1 remains unclear, because it presumably did not evolve to carry out these pathological functions. A new report proposes that 53BP1 activity prevents hyper-resection and thereby promotes error-free DNA repair while suppressing alternative mutagenic pathways.

    • Dali Zong
    • Arnab Ray Chaudhuri
    • André Nussenzweig
    News & Views