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1.600 Aktuelle Fachpublikationen in Genes & Development

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Live-cell imaging reveals the dynamics of PRC2 and recruitment to chromatin by SUZ12-associated subunits [Research Papers]

01.06.2018 | Daniel T. Youmans; Jens C. Schmidt; Thomas R. Cech, Genes & Development, 2018

Polycomb-repressive complex 2 (PRC2) is a histone methyltransferase that promotes epigenetic gene silencing, but the dynamics of its interactions with chromatin are largely unknown. Here we quantitatively measured the binding of PRC2 to chromatin in human cancer cells. Genome editing of a HaloTag ...

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JAK2 is dispensable for maintenance of JAK2 mutant B-cell acute lymphoblastic leukemias [Research Papers]

01.06.2018 | Sang-Kyu Kim; Deborah A. Knight; Lisa R. Jones; Stephin Vervoort; Ashley P. Ng; John F. Seymour; James E. Bradner; M ..., Genes & Development, 2018

Activating JAK2 point mutations are implicated in the pathogenesis of myeloid and lymphoid malignancies, including high-risk B-cell acute lymphoblastic leukemia (B-ALL). In preclinical studies, treatment of JAK2 mutant leukemias with type I JAK2 inhibitors (e.g., Food and Drug Administration ...

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Nucleosomes around a mismatched base pair are excluded via an Msh2-dependent reaction with the aid of SNF2 family ATPase Smarcad1 [Research Papers]

01.06.2018 | Riki Terui; Koji Nagao; Yoshitaka Kawasoe; Kanae Taki; Torahiko L. Higashi; Seiji Tanaka; Takuro Nakagawa; Chikashi ..., Genes & Development, 2018

Post-replicative correction of replication errors by the mismatch repair (MMR) system is critical for suppression of mutations. Although the MMR system may need to handle nucleosomes at the site of chromatin replication, how MMR occurs in the chromatin environment remains unclear. Here, we show ...

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PARD3 dysfunction in conjunction with dynamic HIPPO signaling drives cortical enlargement with massive heterotopia [Research Papers]

01.06.2018 | Wenying Angela Liu; She Chen; Zhizhong Li; Choong Heon Lee; Ghayda Mirzaa; William B. Dobyns; M. Elizabeth Ross; Jia ..., Genes & Development, 2018

Proper organization and orderly mitosis of radial glial progenitors (RGPs) drive the formation of a laminated mammalian cortex in the correct size. However, the molecular underpinnings of the intricate process remain largely unclear. Here we show that RGP behavior and cortical development are ...

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Polycystic kidney disease: a Hippo connection [Outlook]

01.06.2018 | Shenghong Ma; Kun-Liang Guan, Genes & Development, 2018

Mutations in PKD1 and PKD2 are the leading cause of autosomal dominant polycystic kidney disease (ADPKD). In this issue of Genes & Development, a report by Cai and colleagues (pp. 781–793) reveals new insight into the molecular basis by which PKD1 deficiency leads to cystic kidney pathogenesis. ...

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A RhoA-YAP-c-Myc signaling axis promotes the development of polycystic kidney disease [Research Papers]

01.06.2018 | Jing Cai; Xuewen Song; Wei Wang; Terry Watnick; York Pei; Feng Qian; Duojia Pan, Genes & Development, 2018

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder caused by mutations in PKD1 or PKD2 and affects one in 500–1000 humans. Limited treatment is currently available for ADPKD. Here we identify the Hippo signaling effector YAP and its transcriptional target, c-Myc, as ...

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Impaired DNA demethylation of C/EBP sites causes premature aging [Research Papers]

01.06.2018 | Andrea Schäfer; Bernadette Mekker; Medhavi Mallick; Viviana Vastolo; Emil Karaulanov; Dominik Sebastian; Carina von ..., Genes & Development, 2018

Changes in DNA methylation are among the best-documented epigenetic alterations accompanying organismal aging. However, whether and how altered DNA methylation is causally involved in aging have remained elusive. GADD45α (growth arrest and DNA damage protein 45A) and ING1 (inhibitor of growth ...

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lncRNA PAPAS tethered to the rDNA enhancer recruits hypophosphorylated CHD4/NuRD to repress rRNA synthesis at elevated temperatures [Research Papers]

01.06.2018 | Zhongliang Zhao; Nevcin Sentürk; Chenlin Song; Ingrid Grummt, Genes & Development, 2018

Attenuation of pre-rRNA synthesis in response to elevated temperature is accompanied by increased levels of PAPAS ("promoter and pre-rRNA antisense"), a long noncoding RNA (lncRNA) that is transcribed in an orientation antisense to pre-rRNA. Here we show that PAPAS interacts directly with DNA, ...

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Laminating the mammalian cortex during development: cell polarity protein function and Hippo signaling [Outlook]

01.06.2018 | Khadar Abdi; Chay T. Kuo, Genes & Development, 2018

During mammalian brain development, radial glial progenitors balance between proliferation and differentiation to generate the laminated cortical layers in a temporally precise fashion. Defects in the individual steps going into this complex organogenesis can result in cortical malformations and ...

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Separable roles for Mec1/ATR in genome maintenance, DNA replication, and checkpoint signaling [Research Papers]

01.06.2018 | Michael Charles Lanz; Susannah Oberly; Ethan James Sanford; Sushma Sharma; Andrei Chabes; Marcus Bustamante Smolka, Genes & Development, 2018

The Mec1/ATR kinase coordinates multiple cellular responses to replication stress. In addition to its canonical role in activating the checkpoint kinase Rad53, Mec1 also plays checkpoint-independent roles in genome maintenance that are not well understood. Here we used a combined ...

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