BRCA1-associated exclusion of 53BP1 from DNA damage sites underlies temporal control of DNA repair.
AuthorsChapman JR, Sossick AJ, Boulton SJ, Jackson SP,
JournalJ Cell Sci
PubMed ID22553214
'Following irradiation, numerous DNA-damage-responsive proteins rapidly redistribute into microscopically visible subnuclear aggregates, termed ionising-radiation-induced foci (IRIF). How the enrichment of proteins on damaged chromatin actually relates to DNA repair remains unclear. Here, we use super-resolution microscopy to examine the spatial distribution of BRCA1 and 53BP1 proteins within single IRIF at ... More
Quiescent gastric stem cells maintain the adult Drosophila stomach.
AuthorsStrand M, Micchelli CA,
JournalProc Natl Acad Sci U S A
PubMed ID21984734
'The adult Drosophila copper cell region or "stomach" is a highly acidic compartment of the midgut with pH < 3. In this region, a specialized group of acid-secreting cells similar to mammalian gastric parietal cells has been identified by a unique ultrastructure and by copper-metallothionein fluorescence. However, the homeostatic mechanism ... More
Long-term live imaging provides new insight into stem cell regulation and germline-soma coordination in the Drosophila ovary.
AuthorsMorris LX, Spradling AC,
JournalDevelopment
PubMed ID21558370
'The Drosophila ovariole tip produces new ovarian follicles on a 12-hour cycle by controlling niche-based germline and follicle stem cell divisions and nurturing their developing daughters. Static images provide a thumbnail view of folliculogenesis but imperfectly capture the dynamic cellular interactions that underlie follicle production. We describe a live-imaging culture ... More
Histone H3 lysine 4 methylation marks postreplicative human cytomegalovirus chromatin.
AuthorsNitzsche A, Steinhäusser C, Mücke K, Paulus C, Nevels M,
JournalJ Virol
PubMed ID22761369
'In the nuclei of permissive cells, human cytomegalovirus genomes form nucleosomal structures initially resembling heterochromatin but gradually switching to a euchromatin-like state. This switch is characterized by a decrease in histone H3 K9 methylation and a marked increase in H3 tail acetylation and H3 K4 methylation across the viral genome. ... More
Schwann cell myelination requires integration of laminin activities.
'Laminins promote early stages of peripheral nerve myelination by assembling basement membranes (BMs) on Schwann cell surfaces, leading to activation of ß1 integrins and other receptors. The BM composition, structural bonds and ligands needed to mediate this process, however, are not well understood. Mice hypomorphic for laminin ?1-subunit expression that ... More
Distinct roles of the ATR kinase and the Mre11-Rad50-Nbs1 complex in the maintenance of chromosomal stability in Arabidopsis.
AuthorsAmiard S, Charbonnel C, Allain E, Depeiges A, White CI, Gallego ME,
JournalPlant Cell
PubMed ID20876831
'Signaling of chromosomal DNA breaks is of primary importance for initiation of repair and, thus, for global genomic stability. Although the Mre11-Rad50-Nbs1 (MRN) complex is the first sensor of double-strand breaks, its role in double-strand break (DSB) signaling is not fully understood. We report the absence of ?-ray-induced, ATM/ATR-dependent histone ... More
Regulation of Drosophila glial cell proliferation by Merlin-Hippo signaling.
AuthorsReddy BV, Irvine KD,
JournalDevelopment
PubMed ID22069188
'Glia perform diverse and essential roles in the nervous system, but the mechanisms that regulate glial cell numbers are not well understood. Here, we identify and characterize a requirement for the Hippo pathway and its transcriptional co-activator Yorkie in controlling Drosophila glial proliferation. We find that Yorkie is both necessary ... More
Evaluation of 5-ethynyl-2'-deoxyuridine staining as a sensitive and reliable method for studying cell proliferation in the adult nervous system.
AuthorsZeng C, Pan F, Jones LA, Lim MM, Griffin EA, Sheline YI, Mintun MA, Holtzman DM, Mach RH,
JournalBrain Res
PubMed ID20064490
Recently, a novel method for detection of DNA synthesis has been developed based on the incorporation of 5-ethynyl-2'-deoxyuridine (EdU), a thymidine analogue, into cellular DNA and the subsequent reaction of EdU with a fluorescent azide in a copper-catalyzed [3+2] cycloaddition ( ... More
An organotypic coculture model supporting proliferation and differentiation of medullary thymic epithelial cells and promiscuous gene expression.
Understanding intrathymic T cell differentiation has been greatly aided by the development of various reductionist in vitro models that mimic certain steps/microenvironments of this complex process. Most models focused on the faithful in vitro restoration of T cell differentiation and selection. In contrast, suitable in vitro models emulating the developmental ... More
A chemical method for fast and sensitive detection of DNA synthesis in vivo.
AuthorsSalic A, Mitchison TJ,
JournalProc Natl Acad Sci U S A
PubMed ID18272492
We have developed a method to detect DNA synthesis in proliferating cells, based on the incorporation of 5-ethynyl-2'-deoxyuridine (EdU) and its subsequent detection by a fluorescent azide through a Cu(I)-catalyzed [3 + 2] cycloaddition reaction ("click" chemistry). Detection of the EdU label is highly sensitive and can be accomplished in ... More
S-nitrosylation of HDAC2 regulates the expression of the chromatin-remodeling factor Brm during radial neuron migration.
AuthorsNott A, Nitarska J, Veenvliet JV, Schacke S, Derijck AA, Sirko P, Muchardt C, Pasterkamp RJ, Smidt MP, Riccio A,
JournalProc Natl Acad Sci U S A
PubMed ID23359715
Dynamic epigenetic modifications play a key role in mediating the expression of genes required for neuronal development. We previously identified nitric oxide (NO) as a signaling molecule that mediates S-nitrosylation of histone deacetylase 2 (HDAC2) and epigenetic changes in neurons. Here, we show that HDAC2 nitrosylation regulates neuronal radial migration ... More
Retinol dehydrogenase 10 is indispensible for spermatogenesis in juvenile males.
AuthorsTong MH, Yang QE, Davis JC, Griswold MD,
JournalProc Natl Acad Sci U S A
PubMed ID23267101
Retinoic acid (RA), an active vitamin A derivative, is essential for mammalian spermatogenesis. Genetic studies have revealed that oxidation of vitamin A to retinal by retinol dehydrogenase 10 (RDH10) is critical for embryonic RA biosynthesis. However, physiological roles of RDH10 in postnatal RA synthesis remain unclear, given that Rdh10 loss-of-function ... More
Regulation of cyclin D2 expression and degradation by follicle-stimulating hormone during rat granulosa cell proliferation in vitro.
AuthorsHan Y, Xia G, Tsang BK,
JournalBiol Reprod
PubMed ID23349233
Cyclin D2 (CCND2, encoded by Ccnd2) plays an important role in the induction of early-to-mid G1 phase transition and is required for granulosa cell proliferation during ovarian folliculogenesis. In the present study, we investigated the role of follicle-stimulating hormone (FSH) in the regulation of cyclin D2 expression and degradation during ... More
FE65 regulates and interacts with the Bloom syndrome protein in dynamic nuclear spheres - potential relevance to Alzheimer's disease.
AuthorsSchrötter A, Mastalski T, Nensa FM, Neumann M, Loosse C, Pfeiffer K, Magraoui FE, Platta HW, Erdmann R, Theiss C, Uszkoreit J, Eisenacher M, Meyer HE, Marcus K, Müller T,
JournalJ Cell Sci
PubMed ID23572515
The intracellular domain of the amyloid precursor protein (AICD) is generated following cleavage of the precursor by the ?-secretase complex and is involved in membrane to nucleus signaling, for which the binding of AICD to the adapter protein FE65 is essential. Here we show that FE65 knockdown causes a downregulation ... More
Myelin gene regulatory factor is required for maintenance of myelin and mature oligodendrocyte identity in the adult CNS.
AuthorsKoenning M, Jackson S, Hay CM, Faux C, Kilpatrick TJ, Willingham M, Emery B,
JournalJ Neurosci
PubMed ID22956843
Although the transcription factors required for the generation of oligodendrocytes and CNS myelination during development have been relatively well established, it is not known whether continued expression of the same factors is required for the maintenance of myelin in the adult. Here, we use an inducible conditional knock-out strategy to ... More
Arabidopsis ATM and ATR kinases prevent propagation of genome damage caused by telomere dysfunction.
AuthorsAmiard S, Depeiges A, Allain E, White CI, Gallego ME,
JournalPlant Cell
PubMed ID22158468
The ends of linear eukaryotic chromosomes are hidden in nucleoprotein structures called telomeres, and loss of the telomere structure causes inappropriate repair, leading to severe karyotypic and genomic instability. Although it has been shown that DNA damaging agents activate a DNA damage response (DDR), little is known about the signaling ... More
Renal collecting system growth and function depend upon embryonic ?1 laminin expression.
In order to understand the functions of laminins in the renal collecting system, the Lamc1 gene was inactivated in the developing mouse ureteric bud (UB). Embryos bearing null alleles exhibited laminin deficiency prior to mesenchymal tubular induction and either failed to develop a UB with involution of the mesenchyme, or ... More
Coupling of T161 and T14 phosphorylations protects cyclin B-CDK1 from premature activation.
AuthorsCoulonval K, Kooken H, Roger PP,
JournalMol Biol Cell
PubMed ID21900495
Mitosis is triggered by the abrupt dephosphorylation of inhibitory Y15 and T14 residues of cyclin B1-bound cyclin-dependent kinase (CDK)1 that is also phosphorylated at T161 in its activation loop. The sequence of events leading to the accumulation of fully phosphorylated cyclin B1-CDK1 complexes remains unclear. Two-dimensional gel electrophoresis allowed us ... More
Polyamines are implicated in the emergence of the embryo from obligate diapause.
Embryonic diapause is a poorly understood phenomenon of reversible arrest of embryo development prior to implantation. In many carnivores, such as the mink (Neovison vison), obligate diapause characterizes each gestation. Embryo reactivation is controlled by the uterus by mechanisms that remain elusive. Because polyamines are essential regulators of cell proliferation ... More
Notch signaling in stomach epithelial stem cell homeostasis.
AuthorsKim TH, Shivdasani RA,
JournalJ Exp Med
PubMed ID21402740
The mammalian adult gastric epithelium self-renews continually through the activity of stem cells located in the isthmus of individual gland units. Mechanisms facilitating stomach stem and progenitor cell homeostasis are unknown. Here, we show that Notch signaling occurs in the mouse stomach epithelium during development and becomes restricted mainly to ... More
Embryonic multipotent progenitors remodel the Drosophila airways during metamorphosis.
AuthorsPitsouli C, Perrimon N,
JournalDevelopment
PubMed ID20940225
Adult structures in holometabolous insects such as Drosophila are generated by groups of imaginal cells dedicated to the formation of different organs. Imaginal cells are specified in the embryo and remain quiescent until the larval stages, when they proliferate and differentiate to form organs. The Drosophila tracheal system is extensively ... More
Nucleotide excision repair-induced H2A ubiquitination is dependent on MDC1 and RNF8 and reveals a universal DNA damage response.
Chromatin modifications are an important component of the of DNA damage response (DDR) network that safeguard genomic integrity. Recently, we demonstrated nucleotide excision repair (NER)-dependent histone H2A ubiquitination at sites of ultraviolet (UV)-induced DNA damage. In this study, we show a sustained H2A ubiquitination at damaged DNA, which requires dynamic ... More
Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium.
Authors
JournalNat Cell Biol
PubMed ID28394884
Defining the Design Principles of Skin Epidermis Postnatal Growth.
Authors
JournalCell
PubMed ID32259486
A subpopulation of adult skeletal muscle stem cells retains all template DNA strands after cell division.
Authors
JournalCell
PubMed ID22265406
NF1 mutation drives neuronal activity-dependent initiation of optic glioma.
Authors
JournalNature
PubMed ID34040258
Neurotoxic reactive astrocytes are induced by activated microglia.
Authors
JournalNature
PubMed ID28099414
Oxidative stress during mitochondrial biogenesis compromises mtDNA integrity in growing hearts and induces a global DNA repair response.
Authors
JournalNucleic Acids Res
PubMed ID22508755
Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition.
Authors
JournalNat Med
PubMed ID24973920
Peripheral re-localization of constitutive heterochromatin advances its replication timing and impairs maintenance of silencing marks.
Authors
JournalNucleic Acids Res
PubMed ID29750270
Distinct fission signatures predict mitochondrial degradation or biogenesis.
Authors
JournalNature
PubMed ID33953403
Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration.