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241.
The BRIP1 helicase functions independently of BRCA1 in the Fanconi anemia pathway for DNA crosslink repair 总被引:1,自引:0,他引:1
BRIP1 (also called BACH1) is a DEAH helicase that interacts with the BRCT domain of BRCA1 (refs. 1-6) and has an important role in BRCA1-dependent DNA repair and checkpoint functions. We cloned the chicken ortholog of BRIP1 and established a homozygous knockout in the avian B-cell line DT40. The phenotype of these brip1 mutant cells in response to DNA damage differs from that of brca1 mutant cells and more closely resembles that of fancc mutant cells, with a profound sensitivity to the DNA-crosslinking agent cisplatin and acute cell-cycle arrest in late S-G2 phase. These defects are corrected by expression of human BRIP1 lacking the BRCT-interaction domain. Moreover, in human cells exposed to mitomycin C, short interfering RNA-mediated knock-down of BRIP1 leads to a substantial increase in chromosome aberrations, a characteristic phenotype of cells derived from individuals with Fanconi anemia. Because brip1 mutant cells are proficient for ubiquitination of FANCD2 protein, our data indicate that BRIP1 has a function in the Fanconi anemia pathway that is independent of BRCA1 and downstream of FANCD2 activation. 相似文献
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Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer 总被引:25,自引:0,他引:25
Fraga MF Ballestar E Villar-Garea A Boix-Chornet M Espada J Schotta G Bonaldi T Haydon C Ropero S Petrie K Iyer NG Pérez-Rosado A Calvo E Lopez JA Cano A Calasanz MJ Colomer D Piris MA Ahn N Imhof A Caldas C Jenuwein T Esteller M 《Nature genetics》2005,37(4):391-400
CpG island hypermethylation and global genomic hypomethylation are common epigenetic features of cancer cells. Less attention has been focused on histone modifications in cancer cells. We characterized post-translational modifications to histone H4 in a comprehensive panel of normal tissues, cancer cell lines and primary tumors. Using immunodetection, high-performance capillary electrophoresis and mass spectrometry, we found that cancer cells had a loss of monoacetylated and trimethylated forms of histone H4. These changes appeared early and accumulated during the tumorigenic process, as we showed in a mouse model of multistage skin carcinogenesis. The losses occurred predominantly at the acetylated Lys16 and trimethylated Lys20 residues of histone H4 and were associated with the hypomethylation of DNA repetitive sequences, a well-known characteristic of cancer cells. Our data suggest that the global loss of monoacetylation and trimethylation of histone H4 is a common hallmark of human tumor cells. 相似文献
244.
A large number of complex networks are scale-free--that is, they follow a power-law degree distribution. Here we propose that the emergence of many scale-free networks is tied to the efficiency of transport and flow processing across these structures. In particular, we show that for large networks on which flows are influenced or generated by gradients of a scalar distributed on the nodes, scale-free structures will ensure efficient processing, whereas structures that are not scale-free, such as random graphs, will become congested. 相似文献
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Irobi J Van Impe K Seeman P Jordanova A Dierick I Verpoorten N Michalik A De Vriendt E Jacobs A Van Gerwen V Vennekens K Mazanec R Tournev I Hilton-Jones D Talbot K Kremensky I Van Den Bosch L Robberecht W Van Vandekerckhove J Van Broeckhoven C Gettemans J De Jonghe P Timmerman V 《Nature genetics》2004,36(6):597-601
Distal hereditary motor neuropathies are pure motor disorders of the peripheral nervous system resulting in severe atrophy and wasting of distal limb muscles. In two pedigrees with distal hereditary motor neuropathy type II linked to chromosome 12q24.3, we identified the same mutation (K141N) in small heat-shock 22-kDa protein 8 (encoded by HSPB8; also called HSP22). We found a second mutation (K141E) in two smaller families. Both mutations target the same amino acid, which is essential to the structural and functional integrity of the small heat-shock protein alphaA-crystallin. This positively charged residue, when mutated in other small heat-shock proteins, results in various human disorders. Coimmunoprecipitation experiments showed greater binding of both HSPB8 mutants to the interacting partner HSPB1. Expression of mutant HSPB8 in cultured cells promoted formation of intracellular aggregates. Our findings provide further evidence that mutations in heat-shock proteins have an important role in neurodegenerative disorders. 相似文献
248.
Egg and sperm cells (gametes) of the mouse are derived from a founder population of primordial germ cells that are set aside early in embryogenesis. Primordial germ cells arise from the proximal epiblast, a region of the early mouse embryo that also contributes to the first blood lineages of the embryonic yolk sac. Embryonic stem cells differentiate in vitro into cystic structures called embryoid bodies consisting of tissue lineages typical of the early mouse embryo. Because embryoid bodies sustain blood development, we reasoned that they might also support primordial germ cell formation. Here we isolate primordial germ cells from embryoid bodies, and derive continuously growing lines of embryonic germ cells. Embryonic germ cells show erasure of the methylation markers (imprints) of the Igf2r and H19 genes, a property characteristic of the germ lineage. We show that embryoid bodies support maturation of the primordial germ cells into haploid male gametes, which when injected into oocytes restore the somatic diploid chromosome complement and develop into blastocysts. Our ability to derive germ cells from embryonic stem cells provides an accessible in vitro model system for studies of germline epigenetic modification and mammalian gametogenesis. 相似文献
249.
一种Ruminobacter amylophilus 70细胞膜联的新支连淀粉酶被4% Triton X-100提取.其新支连淀粉酶活性存在于70%的硫酸铵沉淀组分中.通过等电聚焦纯化,根据SDS凝胶电泳测定,其新支连淀粉酶的分子量是91.2kDa,其等电点是5.8-5.9.根据另一种淀粉酶活性凝胶电泳的方法测定,其新支连淀粉酶的分子量大约是92.6kDa.在R.amylophilus 70细胞中存在着两种类型的淀粉酶(可溶性淀粉酶和膜联淀粉酶,比如新支连淀粉酶)共同承担分解淀粉的作用. 相似文献
250.
配有钢筋和FRP筋梁的非线性有限元分析 总被引:1,自引:0,他引:1
介绍了配有纤维增强复合材料(FRP)筋和普通钢筋梁的非线性有限元分析,结果表明:配有FRP筋梁的强度较仅配钢筋的梁的强度高,2种筋的复合使用可提高梁的延性. 相似文献