排序方式: 共有5条查询结果,搜索用时 15 毫秒
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Kalay E Yigit G Aslan Y Brown KE Pohl E Bicknell LS Kayserili H Li Y Tüysüz B Nürnberg G Kiess W Koegl M Baessmann I Buruk K Toraman B Kayipmaz S Kul S Ikbal M Turner DJ Taylor MS Aerts J Scott C Milstein K Dollfus H Wieczorek D Brunner HG Hurles M Jackson AP Rauch A Nürnberg P Karagüzel A Wollnik B 《Nature genetics》2011,43(1):23-26
Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation. 相似文献
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Summary A small percentage of SG neurons possessing two separate and complete axons were observed in the lumbosacral spinal cord of the adult cat. Since they are found in small numbers and are structurally similar to single axon SG cells, dual axon cells may represent a developmental aberrancy rather than a functionally distinct cell type.This research was supported by U.S.P.H.S. grant No.NS-16642-01. 相似文献
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Bicknell LS Walker S Klingseisen A Stiff T Leitch A Kerzendorfer C Martin CA Yeyati P Al Sanna N Bober M Johnson D Wise C Jackson AP O'Driscoll M Jeggo PA 《Nature genetics》2011,43(4):350-355
Studies into disorders of extreme growth failure (for example, Seckel syndrome and Majewski osteodysplastic primordial dwarfism type II) have implicated fundamental cellular processes of DNA damage response signaling and centrosome function in the regulation of human growth. Here we report that mutations in ORC1, encoding a subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome. We establish that these mutations disrupt known ORC1 functions including pre-replicative complex formation and origin activation. ORC1 deficiency perturbs S-phase entry and S-phase progression. Additionally, we show that Orc1 depletion in zebrafish is sufficient to markedly reduce body size during rapid embryonic growth. Our data suggest a model in which ORC1 mutations impair replication licensing, slowing cell cycle progression and consequently impeding growth during development, particularly at times of rapid proliferation. These findings establish a novel mechanism for the pathogenesis of microcephalic dwarfism and show a surprising but important developmental impact of impaired origin licensing. 相似文献
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Enomoto R Tanimori T Naito T Yoshida T Yanagita S Mori M Edwards PG Asahara A Bicknell GV Gunji S Hara S Hara T Hayashi S Itoh C Kabuki S Kajino F Katagiri H Kataoka J Kawachi A Kifune T Kubo H Kushida J Maeda S Maeshiro A Matsubara Y Mizumoto Y Moriya M Muraishi H Muraki Y Nakase T Nishijima K Ohishi M Okumura K Patterson JR Sakurazawa K Suzuki R Swaby DL Takano K Takano T Tokanai F Tsuchiya K Tsunoo H Uruma K Watanabe A Yoshikoshi T 《Nature》2002,416(6883):823-826
Protons with energies up to approximately 10(15) eV are the main component of cosmic rays, but evidence for the specific locations where they could have been accelerated to these energies has been lacking. Electrons are known to be accelerated to cosmic-ray energies in supernova remnants, and the shock waves associated with such remnants, when they hit the surrounding interstellar medium, could also provide the energy to accelerate protons. The signature of such a process would be the decay of pions (pi(0)), which are generated when the protons collide with atoms and molecules in an interstellar cloud: pion decay results in gamma-rays with a particular spectral-energy distribution. Here we report the observation of cascade showers of optical photons resulting from gamma-rays at energies of approximately 10(12) eV hitting Earth's upper atmosphere, in the direction of the supernova remnant RX J1713.7-3946. The spectrum is a good match to that predicted by pion decay, and cannot be explained by other mechanisms. 相似文献
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Bicknell LS Bongers EM Leitch A Brown S Schoots J Harley ME Aftimos S Al-Aama JY Bober M Brown PA van Bokhoven H Dean J Edrees AY Feingold M Fryer A Hoefsloot LH Kau N Knoers NV Mackenzie J Opitz JM Sarda P Ross A Temple IK Toutain A Wise CA Wright M Jackson AP 《Nature genetics》2011,43(4):356-359
Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears1?3. Both pre- and post-natal growth are impaired in this disorder, and although microcephaly is often evident, intellect is usually normal in this syndrome. We report here that individuals with this disorder show marked locus heterogeneity, and we identify mutations in five separate genes: ORC1, ORC4, ORC6, CDT1 and CDC6. All of these genes encode components of the pre-replication complex, implicating defects in replication licensing as the cause of a genetic syndrome with distinct developmental abnormalities. 相似文献
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