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The use of an artificial nucleotide for polymerase-based recognition of carcinogenic O6-alkylguanine DNA adducts
(2016)Nucleic Acids ResearchEnzymatic approaches for locating alkylation adducts at single-base resolution in DNA could enable new technologies for understanding carcinogenesis and supporting personalized chemotherapy. Artificial nucleotides that specifically pair with alkylated bases offer a possible strategy for recognition and amplification of adducted DNA, and adduct-templated incorporation of an artificial nucleotide has been demonstrated for a model DNA adduct ...Journal Article -
Non-canonical uracil processing in DNA gives rise to double-strand breaks and deletions: relevance to class switch recombination
(2016)Nucleic Acids ResearchDuring class switch recombination (CSR), antigen-stimulated B-cells rearrange their immunoglobulin constant heavy chain (CH) loci to generate antibodies with different effector functions. CSR is initiated by activation-induced deaminase (AID), which converts cytosines in switch (S) regions, repetitive sequences flanking the CH loci, to uracils. Although U/G mispairs arising in this way are generally efficiently repaired to C/Gs by uracil ...Journal Article -
Engineering a ribozyme cleavage-induced split fluorescent aptamer complementation assay
(2016)Nucleic Acids ResearchHammerhead ribozymes are self-cleaving RNA molecules capable of regulating gene expression in living cells. Their cleavage performance is strongly influenced by intra-molecular loop–loop interactions, a feature not readily accessible through modern prediction algorithms. Ribozyme engineering and efficient implementation of ribozyme-based genetic switches requires detailed knowledge of individual self-cleavage performances. By rational ...Journal Article -
Horizontal Gene Acquisitions, Mobile Element Proliferation, and Genome Decay in the Host-Restricted Plant Pathogen Erwinia Tracheiphila
(2016)Genome Biology and EvolutionModern industrial agriculture depends on high-density cultivation of genetically similar crop plants, creating favorable conditions for the emergence of novel pathogens with increased fitness in managed compared with ecologically intact settings. Here, we present the genome sequence of six strains of the cucurbit bacterial wilt pathogen Erwinia tracheiphila (Enterobacteriaceae) isolated from infected squash plants in New York, Pennsylvania, ...Journal Article -
Human AATF/Che-1 forms a nucleolar protein complex with NGDN and NOL10 required for 40S ribosomal subunit synthesis
(2016)Nucleic Acids ResearchMammalian AATF/Che-1 is essential for embryonic development, however, the underlying molecular mechanism is unclear. By immunoprecipitation of human AATF we discovered that AATF forms a salt-stable protein complex together with neuroguidin (NGDN) and NOL10, and demonstrate that the AATF-NGDN-NOL10 (ANN) complex functions in ribosome biogenesis. All three ANN complex members localize to nucleoli and display a mutual dependence with respect ...Journal Article -
Finding approximate gene clusters with GECKO 3
(2016)Nucleic Acids ResearchGene-order-based comparison of multiple genomes provides signals for functional analysis of genes and the evolutionary process of genome organization. Gene clusters are regions of co-localized genes on genomes of different species. The rapid increase in sequenced genomes necessitates bioinformatics tools for finding gene clusters in hundreds of genomes. Existing tools are often restricted to few (in many cases, only two) genomes, and often ...Journal Article -
Structure of a human pre-40S particle points to a role for RACK1 in the final steps of 18S rRNA processing
(2016)Nucleic Acids ResearchSynthesis of ribosomal subunits in eukaryotes is a complex and tightly regulated process that has been mostly characterized in yeast. The discovery of a growing number of diseases linked to defects in ribosome biogenesis calls for a deeper understanding of these mechanisms and of the specificities of human ribosome maturation. We present the 19 Å resolution cryo-EM reconstruction of a cytoplasmic precursor to the human small ribosomal ...Journal Article -
Dual daughter strand incision is processive and increases the efficiency of DNA mismatch repair
(2016)Nucleic Acids ResearchDNA mismatch repair (MMR) is an evolutionarily-conserved process responsible for the repair of replication errors. In Escherichia coli, MMR is initiated by MutS and MutL, which activate MutH to incise transiently-hemimethylated GATC sites. MMR efficiency depends on the distribution of these GATC sites. To understand which molecular events determine repair efficiency, we quantitatively studied the effect of strand incision on unwinding and ...Journal Article -
Synergy between NMR measurements and MD simulations of protein/RNA complexes: Application to the RRMs, the most common RNA recognition motifs
(2016)Nucleic Acids ResearchRNA recognition motif (RRM) proteins represent an abundant class of proteins playing key roles in RNA biology. We present a joint atomistic molecular dynamics (MD) and experimental study of two RRM-containing proteins bound with their single-stranded target RNAs, namely the Fox-1 and SRSF1 complexes. The simulations are used in conjunction with NMR spectroscopy to interpret and expand the available structural data. We accumulate more than ...Journal Article -
SEX-DETector: A Probabilistic Approach to Study Sex Chromosomes in Non-Model Organisms
(2016)Genome Biology and EvolutionWe propose a probabilistic framework to infer autosomal and sex-linked genes from RNA-seq data of a cross for any sex chromosome type (XY, ZW, and UV). Sex chromosomes (especially the non-recombining and repeat-dense Y, W, U, and V) are notoriously difficult to sequence. Strategies have been developed to obtain partially assembled sex chromosome sequences. Most of them remain difficult to apply to numerous non-model organisms, either ...Journal Article