Cell
The ATR-X syndrome is an X-linked disorder comprising severe psychomotor retardation, characteristic facial features, genital abnormalities, and a-thalassemia. We have shown that ATR-X results from diverse mutations of XH2, a member of a subgroup of the helicase superfamily that includes proteins involved in a wide range of cellular functions, including DNA recombination and repair (RAD16, RAD54,...
Nucleotide excision repair is the principal way by which human cells remove UV damage from DNA. Human cell extracts were fractionated to locate active components, including xeroderma pigmentosum (XP) and ERCC factors. The incision reaction was then reconstituted with the purified proteins RPA, XPA, TFIIH (containing XPB and XPD), XPC, UV-DDB, XPG, partially purified ERCC1/XPF complex, and a factor...
Signaling by TGFβ-related factors requires ligand-induced association between type I and type II transmembrane serine/threonine kinases. In Drosophila, the saxophone (sax) and thick veins (tkv) genes encode type I receptors that mediate signaling by decapentaplegic (dpp), a member of the bone morphogenetic protein (BMP) subgroup of TGFβ-type factors. In this report, we demonstrate that the Drosophila...
Growth and patterning of the vertebrate limb are controlled by the ridge, posterior mesenchyme, and nonridge ectoderm. Fibroblast growth factor 4 (FGF4) and Sonic hedgehog (SHH) can mediate signaling from the ridge and posterior mesenchyme, respectively. Here we show that dorsal ectoderm is required together with FGF4 to maintain Shh expression. Removal of dorsal ectoderm results in loss of posterior...
The initial steps of pattern formation in the developing Drosophila eye involve the coordination of cell cycles, changes in cell shape, and the specification of the R8 photoreceptor cell. These events begin several cell rows ahead of the morphogenetic furrow and are positively regulated by secreted signaling proteins and the proneural HLH transcription factor atonal (ato). Two HLH regulatory proteins...
Here we report the isolation of a rat cDNA clone, Jagged, which we show encodes a ligand for vertebrate Notch. Our conclusion is based on three observations. First, sequence analysis reveals substantial homology between Jagged and invertebrate ligands for the LIN-12/Notch proteins. Second, in situ hybridization of rat embryos identifies both distinct and overlapping patterns of gene expression for...
TGFβ elicits diverse cellular responses by signaling through receptor complexes formed by two distantly related transmembrane serine/threonine kinases called type II and type I receptors. Previous studies have indicated that the product of the Drosophila thick veins (tkv) gene is a type I receptor for decapentaplegic (dpp). Here, we show that the Drosophila gene punt encodes a homolog of a vertebrate...
Crystal structures of the DNA repair enzyme human uracil-DNA glycosylase (UDG), combined with mutational analysis, reveal the structural basis for the specificity of the enzyme. Within the classic α/β fold of UDG, sequence-conserved residues form a positively charged, active-site groove the width of duplex DNA, at the C-terminal edge of the central four-stranded parallel β sheet. In the UDG-6-aminouracil...
The vegetative and reproductive (flowering) phases of Arabidopsis development are clearly separated. The onset of flowering is promoted by long photoperiods, but the constans (co) mutant flowers later than wild type under these conditions. The CO gene was isolated, and two zinc fingers that show a similar spacing of cysteines, but little direct homology, to members of the GATA1 family were identified...
C 2 domains are regulatory sequence motifs that occur widely in nature. Synaptotagmin I, a synaptic vesicle protein involved in the Ca 2 + regulation of exocytosis, contains two C 2 domains, the first of which acts as a Ca 2 + sensor. We now describe the three-dimensional structure of this C 2 domain at 1.9 A resolution in both the Ca 2 + ...
Xklp1 is a novel Xenopus kinesin-like protein with a motor domain at the amino terminus, nuclear localization sequences in the stalk, and a putative zinc fingerlike sequence in the tail. It is nuclear during interphase and chromosomal during mitosis. During late anaphase, a fraction of the protein relocalizes to the spindle interzone and accumulates in the midbody during telophase. Depletion of Xklp1...
X-linked recessive chondrodysplasia punctata (CDPX) is a congenital defect of bone and cartilage development characterized by aberrant bone mineralization, severe underdevelopment of nasal cartilage, and distal phalangeal hypoplasia. A virtually identical phenotype is observed in the warfarin embryopathy, which is due to the teratogenic effects of coumarin derivatives during pregnancy. We have cloned...
Limb-girdle muscular dystrophies (LGMDs) are a group of inherited diseases whose genetic etiology has yet to be elucidated. The autosomal recessive forms (LGMD2) constitute a genetically heterogeneous group with LGMD2A mapping to chromosome 15815.1–821.1. The gene encoding the muscle-specific calcium-activated neutral protease 3 (CANP3) large subunit is located in this region. This cysteine protease...