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The crystal structure of the FACT histone chaperone domain Spt16M in complex with the H2A–H2B heterodimer is solved; Spt16M makes several interactions with histones and seems to block the interaction of H2B with DNA, which could explain how FACT destabilizes nucleosomes to promote transcription.

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.

In bilaterian animals, the final configurations of central nervous systems seem unrelated to neuroectodermal patterning systems, so it is likely that the various architectures of the ventral nerve cords evolved convergently, many times.

The human histone macroH2A.1.1 recruits activated PARP1 enzyme to chromatin through its poly(ADP-ribose)-binding macrodomain. New work shows that PARP1 and CBP can be displaced from chromatin in cancer cells that have lost macroH2A.1.1, thus leading to changes in histone H2B acetylation at cancer-relevant genes.

Cells employ global genome nucleotide excision repair to repair a broad spectrum of genomic DNA lesions. Here, the authors reveal how chromatin is primed for repair, providing insight into mechanisms of chromatin plasticity during DNA repair.

In this study, the authors present a cellular assay to probe macrodomain ADP-ribosylhydrolase activity. This relies on PARP15, forming nuclear foci upon automodification, which are dissolved by loss of MARylation. The system enables functional studies and screening of macrodomain and PARP15 inhibitors in physiologically relevant conditions, capturing cell permeability and cytotoxicity.

Chromatin-remodeling enzymes perform the formidable task of reorganizing the structure of a stable macromolecular assembly, the nucleosome. Recently published work demonstrates that the SNF2H chromatin remodeler distorts the histone octamer structure upon binding to the nucleosome, then taps into this induced plasticity to productively achieve nucleosome sliding.

MacroH2A histone variants originated before the split of fungi and animals. ADP-ribose binding is an ancestral feature of their macrodomains and is linked to the compartmental regulation of NAD metabolism. This function was selected for during the evolution of metazoans.

ADP-ribosylation catalyzed by PARPs and sirtuins is an important post-translation modification. Macrodomain proteins MacroD1 and D2 are now shown to preferentially bind mono-ADP-ribosylated proteins and to act as proximal ADP-ribosylhydrolases. The crystal structure of the MacroD2–ADPr complex suggests a catalytic mechanism for the reaction.

rDNA repeats residing in the nucleolus must be released to the nucleoplasm to allow repair by homologous recombination. Here the authors reveal insights into the molecular mechanism proposing that phosphorylation and SUMOylation of the rDNA-tethering complex facilitate the nucleolar release of damaged repeats to maintain genome integrity.

A recent report shows that several 'poly-ADP-ribose-polymerases' may function exclusively as a family of endogenous mono-ADP-ribosyltransferases, providing a new, molecularly less complex and broadened cellular role for this elusive post-translational modification.

PARP1 is activated by sensing DNA damage, forming ADP-ribose chains that recruit DNA repair and chromatin remodeling factors. PARP1 recognizes DNA damage through its DNA-binding domain, which contains two zinc-finger regions (ZnF1 and ZnF2). The crystal structure of human PARP1-DBD bound to a DNA break reveals a dimeric arrangement, in which ZnF1 from one monomer interacts with ZnF2 from the other monomer, to recognize the DNA strand break.

The role of wild and domesticated animals on alpine ecosystems is unclear. Here, the authors use sedaDNA from 14 European alpine lakes to demonstrate a positive association between wild and domesticated animal and plant diversity through the past 14 thousand years.

Poly-ADP-ribosylation is a post-translational modification catalyzed by enzymes such as PARP1, which responds to metabolic and genotoxic stress. Now macrodomain-containing proteins are shown to rapidly move to PARP1 activation sites, and recruitment of the macrodomain-containing histone macroH2A1.1 results in local chromatin changes.

Poly-(ADP-ribosylation) is a post-translational modification with broad roles in cell signaling. A recently reported crystal structure reveals how the accessory factor HPF1 extends the catalytic active site of PARP1 and PARP2 to promote the specific ADP-ribosylation of serine residues, a prerequisite for dynamic chromatin changes induced by DNA damage.

Pioneer transcription factors access gene regulatory sites embedded within chromatin. They drive gene expression programs vital for cell fate decisions and cellular reprogramming, but how they engage nucleosomal sites at the molecular level is unclear. New results show that they engage histones and collaborate to overcome the nucleosome barrier.

Histone variant macroH2A1.1 inhibits PARP activity to maintain mitochondrial NAD⁺ pools in muscle cells, thus linking chromatin state to optimal energy metabolism.

A new study shows that CtBP, a transcription corepressor, may mediate its effect by blocking histone acetylation, a mark of active transcription. This activity is modulated by NADH binding, thereby supporting a link between cellular metabolism and gene expression.