Heterochromatin mainly comprises repeated DNA sequences that are prone to ectopic recombination. In Drosophila cells, 'safe' repair of heterochromatic double-strand breaks by homologous recombination relies on the relocalization of repair sites to the nuclear periphery before strand invasion. The mechanisms responsible for this movement were unknown. Here we show that relocalization occurs by directed motion along nuclear actin filaments assembled at repair sites by the Arp2/3 complex. Relocalization requires nuclear myosins associated with the heterochromatin repair complex Smc5/6 and the myosin activator Unc45, which is recruited to repair sites by Smc5/6. ARP2/3, actin nucleation and myosins also relocalize heterochromatic double-strand breaks in mouse cells. Defects in this pathway result in impaired heterochromatin repair and chromosome rearrangements. These findings identify de novo nuclear actin filaments and myosins as effectors of chromatin dynamics for heterochromatin repair and stability in multicellular eukaryotes.

TSPO, a stress-induced, posttranslationally regulated, early secretory pathway-localized plant cell membrane protein, belongs to the TspO/MBR family of regulatory proteins, which can bind porphyrins. This work finds that boosting tetrapyrrole biosynthesis enhanced TSPO degradation in Arabidopsis thaliana and that TSPO could bind heme in vitro and in vivo. This binding required the His residue at position 91 (H91), but not that at position 115 (H115). The H91A and double H91A/H115A substitutions stabilized TSPO and rendered the protein insensitive to heme-regulated degradation, suggesting that heme binding regulates At-TSPO degradation. TSPO degradation was inhibited in the autophagy-defective atg5 mutant and was sensitive to inhibitors of type III phosphoinositide 3-kinases, which regulate autophagy in eukaryotic cells. Mutation of the two Tyr residues in a putative ubiquitin-like ATG8 interacting motif of At-TSPO did not affect heme binding in vitro but stabilized the protein in vivo, suggesting that downregulation of At-TSPO requires an active autophagy pathway, in addition to heme. Abscisic acid-dependent TSPO induction was accompanied by an increase in unbound heme levels, and downregulation of TSPO coincided with the return to steady state levels of unbound heme, suggesting that a physiological consequence of active TSPO downregulation may be heme scavenging. In addition, overexpression of TSPO attenuated aminolevulinic acid-induced porphyria in plant cells. Taken together, these data support a role for TSPO in porphyrin binding and scavenging during stress in plants.

Concentrating factors in nuclear bodies is thought to promote efficient gene expression. Tatomer et al. show that the histone locus body (HLB) concentrates pre-mRNA processing factors at replication-dependent histone genes, resulting in optimal 3′ end formation of histone mRNAs coupled with transcription termination.

BackgroundThe underlying cellular and molecular mechanisms that coordinate the physiological processes in digestion are complex, cryptic, and involve the integration of multiple cellular and organ systems. In all intestines, peristaltic action of the gut moves food through the various stages of digestion from the anterior end towards the posterior, with the rate of flow dependent on signals, both intrinsic and extrinsic to the gut itself.ResultsWe have identified an enteroendocrine cell type that regulates gut motility in the Drosophila melanogaster larval midgut. These cells are located at the junction of the anterior and the acidic portions of the midgut and are a group of enteroendocrine cells that express the peptide hormone Diuretic Hormone 31 in this region of the gut. Using cell ablation and ectopic activation via expression of the Chlamydomonas reinhardtii blue light-activated channelopsin, we demonstrate that these enteroendocrine cells are both necessary and sufficient for the peristalsis in the junction region of the midgut and require the Diuretic Hormone 31 to affect normal peristalsis in this region. Within the same junction region of the midgut, we have also identified morphological features suggesting that this region acts as a valve that regulates the transit of food from the anterior midgut into the acidic portion of the gut.ConclusionsWe have characterized and described a set of enteroendocrine cells called the Midgut Junction DH31 expressing cells that are required for peristaltic movement in the junction region between the anterior portion and acidic region of the larval midgut of Drosophila melanogaster. We have shown that the Midgut Junction DH31 expressing cells are necessary and sufficient for motility and that the peptide hormone DH31 is required for peristalsis in the junction region of the midgut. The Drosophila model system will allow for a further dissection of the digestion process and provide a better understanding of the mechanisms that regulate digestion in all organisms.

Heterochromatin is mostly composed of repeated DNA sequences prone to aberrant recombination. How cells maintain the stability of these sequences during double-strand break (DSB) repair has been a long-standing mystery. Studies in Drosophila cells revealed that faithful homologous recombination repair of heterochromatic DSBs relies on the striking relocalization of repair sites to the nuclear periphery before Rad51 recruitment and repair progression. Here, we summarize our current understanding of this response, including the molecular mechanisms involved, and conserved pathways in mammalian cells. We will highlight important similarities with pathways identified in budding yeast for repair of other types of repeated sequences, including rDNA and short telomeres. We will also discuss the emerging role of chromatin composition and regulation in heterochromatin repair progression. Together, these discoveries challenged previous assumptions that repair sites are substantially static in multicellular eukaryotes, that heterochromatin is largely inert in the presence of DSBs, and that silencing and compaction in this domain are obstacles to repair.This article is part of the themed issue ‘Chromatin modifiers and remodellers in DNA repair and signalling’.