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Molecular Cell

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  1. Loss of MBNL Leads to Disruption of Developmentally Regulated Alternative Polyadenylation in RNA-Mediated Disease

    Molecular Cell 56(2):311 (2014)

    We report that depletion of Mbnl proteins in mouse embryo fibroblasts leads to misregulation of thousands of alternative polyadenylation events. HITS-CLIP and minigene reporter analyses indicate that these polyadenylation switches are a direct consequence of MBNL binding to target RNAs. Misregulated...
  2. Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide: implications for signaling.

    Molecular Cell 14(3):405 (2004) PMID 15125843

    We report the crystal structure of the BRCT repeats of human BRCA1 bound to a phosphorylated BACH1 peptide at 2.3 A resolution. The phosphorylated serine 990 and phenylalanine 993 of BACH1 anchor the binding to BRCA1 through specific interactions with a surface cleft at the junction of the two BRCT...
  3. Structural basis for octameric ring formation and DNA interaction of the human homologous-pairing protein Dmc1.

    Molecular Cell 14(3):363 (2004) PMID 15125839

    We crystallized the full-length human Dmc1 protein and solved the structure of the Dmc1 octameric ring. The monomeric structure of the Dmc1 protein closely resembled those of the human and archaeal Rad51 proteins. In addition to the polymerization motif that was previously identified in the Rad51 pr...
  4. Mitotic checkpoint inactivation fosters transformation in cells lacking the breast cancer susceptibility gene, Brca2.

    Molecular Cell 4(1):1 (1999) PMID 10445022

    We report that inactivation of cell cycle checkpoints responsive to mitotic spindle disruption, by mutant forms of p53 or Bub1, relieves growth arrest and initiates neoplastic transformation in primary cells homozygous for truncated Brca2. Tumors from Brca2-deficient animals exhibit dysfunction of t...
  5. A global regulatory mechanism for activating an exon network required for neurogenesis.

    Molecular Cell 56(1):90 (2014) PMID 25219497

    We demonstrate that nSR100-dependent neural exons are associated with a unique configuration of intronic cis-elements that promote rapid switch-like regulation during neurogenesis. A key feature of this configuration is the insertion of specialized intronic enhancers between polypyrimidine tracts an...
  6. eRNAs Lure NELF from Paused Polymerases.

    Molecular Cell 56(1):3 (2014) PMID 25280099

    RNAs transcribed from enhancers (eRNAs) have been linked to enhancer function. In this issue of Molecular Cell, Schaukowitch et al. (2014) show that upon activation, eRNAs can bind NELF and are necessary for its transient removal from promoters to release paused RNA polymerase II and drive expressio...
  7. NuA4 Initiates Dynamic Histone H4 Acetylation to Promote High-Fidelity Sister Chromatid Recombination at Postreplication Gaps

    Molecular Cell 55(6):818 (2014) PMID 25132173 PMCID PMC4169719

    We discovered that regulated histone H4 acetylation is required to maintain CAG repeat stability and promote gap-induced sister chromatid recombination. CAG expansions in the absence of H4 HATs NuA4 and Hat1 and HDACs Sir2, Hos2, and Hst1 depended on Rad52, Rad57, and Rad5 and were therefore arising...
  8. Reconstitution of a minimal ribosome-associated ubiquitination pathway with purified factors.

    Molecular Cell 55(6):880 (2014) PMID 25132172 PMCID PMC4175178

    We reconstitute ribosome-associated ubiquitination with purified factors to define the minimal components and essential steps in this process. We find that the primary role of the ribosome splitting factors Hbs1, Pelota, and ABCE1 is to permit Listerin access to the nascent chain. Listerin alone can...
  9. Maternal Aldehyde Elimination during Pregnancy Preserves the Fetal Genome.

    Molecular Cell 55(6):807 (2014) PMID 25155611 PMCID PMC4175174

    We discover how the embryo is protected from these genotoxins. Pregnant mice lacking Aldh2, a key enzyme that detoxifies reactive aldehydes, cannot support the development of embryos lacking the Fanconi anemia DNA repair pathway gene Fanca. Remarkably, transferring Aldh2(-/-)Fanca(-/-) embryos into...
  10. The long noncoding RNAs NEAT1 and MALAT1 bind active chromatin sites.

    Molecular Cell 55(5):791 (2014) PMID 25155612

    We mapped the genomic binding sites for two highly expressed human lncRNAs, NEAT1 and MALAT1. We show that NEAT1 and MALAT1 localize to hundreds of genomic sites in human cells, primarily over active genes. NEAT1 and MALAT1 exhibit colocalization to many of these loci, but display distinct gene body...