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• Meiotic chromosome pairing between homoeologous chromosomes was reported in many nascent allopolyploids. Homoeologous pairing is gradually eliminated and replaced by exclusive homologous pairing in well-established allopolyploids, an evolutionary process referred to as the diploidization of allopolyploids. A fundamental question of the diploidization of allopolyploids is whether and to what extent the DNA sequence variation among homoeologous chromosomes contribute to the establishment of exclusive homologous chromosome pairing. • We developed aneuploid tetraploid maize lines that contain three copies of chromosome 10 derived from inbred lines B73 and H99. We were able to identify the parental origin of each copy of chromosome 10 in the materials using oligonucleotide-based haplotype-specific chromosome painting. • We demonstrate that the two identical copies of chromosome 10 from H99 pair preferentially over chromosome 10 from B73 in different stages of prophase I and metaphase I during meiosis. Thus, homologous chromosome pairing is favored to partners with the most similar DNA sequences and can be discriminated based on cryptic sequence variation. • We propose that innate preference of homologous chromosome pairing exists in nascent allopolyploids and serves as the first layer that would eventually block all homoeologous chromosome pairing in allopolyploids.

The tumour suppressor complex BRCA1–BARD1 functions in the repair of DNA double-stranded breaks by homologous recombination. During this process, BRCA1–BARD1 facilitates the nucleolytic resection of DNA ends to generate a single-stranded template for the recruitment of another tumour suppressor complex, BRCA2–PALB2, and the recombinase RAD51. Here, by examining purified wild-type and mutant BRCA1–BARD1, we show that both BRCA1 and BARD1 bind DNA and interact with RAD51, and that BRCA1–BARD1 enhances the recombinase activity of RAD51. Mechanistically, BRCA1–BARD1 promotes the assembly of the synaptic complex, an essential intermediate in RAD51-mediated DNA joint formation. We provide evidence that BRCA1 and BARD1 are indispensable for RAD51 stimulation. Notably, BRCA1–BARD1 mutants with weakened RAD51 interactions show compromised DNA joint formation and impaired mediation of homologous recombination and DNA repair in cells. Our results identify a late role of BRCA1–BARD1 in homologous recombination, an attribute of the tumour suppressor complex that could be targeted in cancer therapy. The tumour suppressor complex BRCA1–BARD1, which facilitates the generation of a single-stranded DNA template during homologous recombination, also binds to the recombinase RAD51 and enhances its function. Expanded role for BRCA1 in DNA repair Two of the hereditary breast cancer susceptibility genes (BRCAs) act during the initial stages of recombinational DNA repair. BRCA1, together with BARD1, helps to form the single-stranded DNA that is then bound by another complex, BRCA2–PALB2, which facilitates loading of the central DNA strand exchange factor, RAD51. Patrick Sung and colleagues now show that BRCA1–BARD1 can also directly interact with RAD51 and stimulate the formation of the synaptic complex—a crucial intermediate that aligns the damaged and repair template DNA molecules. Because cancer cells depend on functioning DNA repair to thrive, targeting these factors may provide therapeutic value.

Synaptic activity in neurons leads to the rapid activation of genes involved in mammalian behavior. ATP-dependent chromatin remodelers such as the BAF complex contribute to these responses and are generally thought to activate transcription. However, the mechanisms keeping such “early activation” genes silent have been a mystery. In the course of investigating Mendelian recessive autism, we identified six families with segregating loss-of-function mutations in the neuronal BAF (nBAF) subunit ACTL6B (originally named BAF53b). Accordingly, ACTL6B was the most significantly mutated gene in the Simons Recessive Autism Cohort. At least 14 subunits of the nBAF complex are mutated in autism, collectively making it a major contributor to autism spectrum disorder (ASD). Patient mutations destabilized ACTL6B protein in neurons and rerouted dendrites to the wrong glomerulus in the fly olfactory system. Humans and mice lacking ACTL6B showed corpus callosum hypoplasia, indicating a conserved role for ACTL6B in facilitating neural connectivity. Actl6b knockout mice on two genetic backgrounds exhibited ASD-related behaviors, including social and memory impairments, repetitive behaviors, and hyperactivity. Surprisingly, mutation of Actl6b relieved repression of early response genes including AP1 transcription factors (Fos, Fosl2, Fosb, and Junb), increased chromatin accessibility at AP1 binding sites, and transcriptional changes in late response genes associated with early response transcription factor activity. ACTL6B loss is thus an important cause of recessive ASD, with impaired neuronspecific chromatin repression indicated as a potential mechanism.

The choice of the elliptic curve for a given pairing based protocol is primordial. For many cryptosystems based on pairings such as group signatures and their variants (EPID, anonymous attestation, etc) or accumulators, operations in the first pairing group G of points of the elliptic curve is more predominant. At 128-bit security level two curves BW13-P310 and BW19-P286 with odd embedding degrees 13 and 19 suitable for super optimal pairing have been recommended for such pairing based protocols. But a prime embedding degree (k=13;19) eliminates some important optimisation for the pairing computation. However The Miller loop length of the superoptimal pairing is the half of that of the optimal ate pairing but involve more exponentiations that affect its efficiency. In this work, we successfully develop methods and construct algorithms to efficiently evaluate and avoid heavy exponentiations that affect the efficiency of the superoptimal pairing. This leads to the definition of new bilinear and non degenerate pairing on BW13-P310 and BW19-P286 called x-superoptimal pairing where its Miller loop is about 15.3% and 39.8% faster than the one of the optimal ate pairing previously computed on BW13-P310 and BW19-P286 respectively.

Hfq‐binding small RNAs (sRNAs) in bacteria modulate the stability and translational efficiency of target mRNAs through limited base‐pairing interactions. While these sRNAs are known to regulate numerous mRNAs as part of stress responses, what distinguishes targets and non‐targets among the mRNAs predicted to base pair with Hfq‐binding sRNAs is poorly understood. Using the Hfq‐binding sRNA Spot 42 of Escherichia coli as a model, we found that predictions using only the three unstructured regions of Spot 42 substantially improved the identification of previously known and novel Spot 42 targets. Furthermore, increasing the extent of base‐pairing in single or multiple base‐pairing regions improved the strength of regulation, but only for the unstructured regions of Spot 42. We also found that non‐targets predicted to base pair with Spot 42 lacked an Hfq‐binding site, folded into a secondary structure that occluded the Spot 42 targeting site, or had overlapping Hfq‐binding and targeting sites. By modifying these features, we could impart Spot 42 regulation on non‐target mRNAs. Our results thus provide valuable insights into the requirements for target selection by sRNAs. Target recognition by bacterial small RNAs is not well understood. The accessibility of the targeted sequences, stability of the duplex, and the binding and positioning of the RNA chaperone Hfq on the mRNA are critical.

Autopolyploidy is more common in plants than traditionally assumed, but has received little attention compared with allopolyploidy. Hence, the advantages and disadvantages of genome doubling per se compared with genome doubling coupled with hybridizations in allopolyploids remain unclear. Autopolyploids are characterized by genomic redundancy and polysomic inheritance, increasing effective population size. To shed light on the evolutionary consequences of autopolyploidy, we review a broad range of studies focusing on both synthetic and natural autopolyploids encompassing levels of biological organization from genes to evolutionary lineages. The limited evidence currently available suggests that autopolyploids neither experience strong genome restructuring nor wide reorganization of gene expression during the first generations following genome doubling, but that these processes may become more important in the longer term. Biogeographic and ecological surveys point to an association between the formation of autopolyploid lineages and environmental change. We thus hypothesize that polysomic inheritance may provide a short-term evolutionary advantage for autopolyploids compared to diploid relatives when environmental change enforces range shifts. In addition, autopolyploids should possess increased genome flexibility, allowing them to adapt and persist across heterogeneous landscapes in the long run.

During meiosis, chromosomes exhibit dramatic changes in morphology and intranuclear positioning. How these changes influence homolog pairing, alignment, and recombination remain elusive. Using Hi-C, we systematically mapped 3D genome architecture throughout all meiotic prophase substages during mouse spermatogenesis. Our data uncover two major chromosome organizational features varying along the chromosome axis during early meiotic prophase, when homolog alignment occurs. First, transcriptionally active and inactive genomic regions form alternating domains consisting of shorter and longer chromatin loops, respectively. Second, the force-transmitting LINC complex promotes the alignment of ends of different chromosomes over a range of up to 20% of chromosome length. Both features correlate with the pattern of homolog interactions and the distribution of recombination events. Collectively, our data reveal the influences of transcription and force on meiotic chromosome structure and suggest chromosome organization may provide an infrastructure for the modulation of meiotic recombination in higher eukaryotes. During meiosis, chromosomes undergo dramatic changes in morphology and intranuclear positioning. Here the authors mapped the 3D genome architecture throughout mouse spermatogenesis by Hi-C of sorted cells to reveal the contributions of transcriptional activity and mechanical force in modulating homolog alignment and recombination.

The majority of base pairs in double-stranded DNA exist in the canonical Watson-Crick geometry. However, they can also adopt alternate Hoogsteen conformations in various complexes of DNA with proteins and small molecules, which are key for biological function and mechanism. While detection of Hoogsteen base pairs in large DNA complexes and assemblies poses considerable challenges for traditional structural biology techniques, we show here that multidimensional dynamic nuclear polarization–enhanced solid-state NMR can serve as a unique spectroscopic tool for observing and distinguishing Watson-Crick and Hoogsteen base pairs in a broad range of DNA systems based on characteristic NMR chemical shifts and internuclear dipolar couplings. We illustrate this approach using a model 12-mer DNA duplex, free and in complex with the antibiotic echinomycin, which features two central adenine-thymine base pairs with Watson-Crick and Hoogsteen geometry, respectively, and subsequently extend it to the ∼200 kDa Widom 601 DNA nucleosome core particle.