Read by QxMD icon Read


Elisabet Einarsdottir, Idor Svensson, Fahimeh Darki, Myriam Peyrard-Janvid, Jessica M Lindvall, Adam Ameur, Christer Jacobsson, Torkel Klingberg, Juha Kere, Hans Matsson
Developmental dyslexia is the most common learning disorder in children. Problems in reading and writing are likely due to a complex interaction of genetic and environmental factors, resulting in reduced power of studies of the genetic factors underlying developmental dyslexia. Our approach in the current study was to perform exome sequencing of affected and unaffected individuals within an extended pedigree with a familial form of developmental dyslexia. We identified a two-base mutation, causing a p.R229L amino acid substitution in the centrosomal protein 63 kDa (CEP63), co-segregating with developmental dyslexia in this pedigree...
November 2015: Human Genetics
Andrew Kodani, Timothy W Yu, Jeffrey R Johnson, Divya Jayaraman, Tasha L Johnson, Lihadh Al-Gazali, Lāszló Sztriha, Jennifer N Partlow, Hanjun Kim, Alexis L Krup, Alexander Dammermann, Nevan J Krogan, Christopher A Walsh, Jeremy F Reiter
Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14...
2015: ELife
Marko Marjanović, Carlos Sánchez-Huertas, Berta Terré, Rocío Gómez, Jan Frederik Scheel, Sarai Pacheco, Philip A Knobel, Ana Martínez-Marchal, Suvi Aivio, Lluís Palenzuela, Uwe Wolfrum, Peter J McKinnon, José A Suja, Ignasi Roig, Vincenzo Costanzo, Jens Lüders, Travis H Stracker
CEP63 is a centrosomal protein that facilitates centriole duplication and is regulated by the DNA damage response. Mutations in CEP63 cause Seckel syndrome, a human disease characterized by microcephaly and dwarfism. Here we demonstrate that Cep63-deficient mice recapitulate Seckel syndrome pathology. The attrition of neural progenitor cells involves p53-dependent cell death, and brain size is rescued by the deletion of p53. Cell death is not the result of an aberrant DNA damage response but is triggered by centrosome-based mitotic errors...
2015: Nature Communications
Deborah J Morris-Rosendahl, Angela M Kaindl
The impact that next-generation sequencing technology (NGS) is having on many aspects of molecular and cell biology, is becoming increasingly apparent. One of the most noticeable outcomes of the new technology in human genetics, has been the accelerated rate of identification of disease-causing genes. Especially for rare, heterogeneous disorders, such as autosomal recessive primary microcephaly (MCPH), the handful of genes previously known to harbour disease-causing mutations, has grown at an unprecedented rate within a few years...
October 2015: Molecular and Cellular Probes
Lina Ma, Ian Quigley, Heymut Omran, Chris Kintner
Multiciliate cells employ hundreds of motile cilia to produce fluid flow, which they nucleate and extend by first assembling hundreds of centrioles. In most cells, entry into the cell cycle allows centrioles to undergo a single round of duplication, but in differentiating multiciliate cells, massive centriole assembly occurs in G0 by a process initiated by a small coiled-coil protein, Multicilin. Here we show that Multicilin acts by forming a ternary complex with E2f4 or E2f5 and Dp1 that binds and activates most of the genes required for centriole biogenesis, while other cell cycle genes remain off...
July 1, 2014: Genes & Development
Elif Nur Firat-Karalar, Navin Rauniyar, John R Yates, Tim Stearns
The centrosome consists of a pair of centrioles and surrounding pericentriolar material (PCM). Many vertebrate cells also have an array of granules, termed centriolar satellites, that localize around the centrosome and are associated with centrosome and cilium function. Centriole duplication occurs once per cell cycle and is effected by a set of proteins including PLK4, CEP192, CEP152, CEP63, and CPAP. Information on the relationships between these components is limited due to the difficulty in assaying interactions in the context of the centrosome...
March 17, 2014: Current Biology: CB
Huijie Zhao, Lei Zhu, Yunlu Zhu, Jingli Cao, Shanshan Li, Qiongping Huang, Tao Xu, Xiao Huang, Xiumin Yan, Xueliang Zhu
Dense multicilia in higher vertebrates are important for luminal flow and the removal of thick mucus. To generate hundreds of basal bodies for multiciliogenesis, specialized terminally differentiated epithelial cells undergo massive centriole amplification. In proliferating cells, however, centriole duplication occurs only once per cell cycle. How cells ensure proper regulation of centriole biogenesis in different contexts is poorly understood. We report that the centriole amplification is controlled by two duplicated genes, Cep63 and Deup1...
December 2013: Nature Cell Biology
Nicola J Brown, Marko Marjanović, Jens Lüders, Travis H Stracker, Vincenzo Costanzo
Centrosomes consist of two centrioles embedded in pericentriolar material and function as the main microtubule organising centres in dividing animal cells. They ensure proper formation and orientation of the mitotic spindle and are therefore essential for the maintenance of genome stability. Centrosome function is crucial during embryonic development, highlighted by the discovery of mutations in genes encoding centrosome or spindle pole proteins that cause autosomal recessive primary microcephaly, including Cep63 and Cep152...
2013: PloS One
Ambuj Kumar, Vidya Rajendran, Rao Sethumadhavan, Rituraj Purohit
Centrosome forms the backbone of cell cycle progression mechanism. Recent debates have occurred regarding the essentiality of centrosome in cell cycle regulation. CEP family protein is the active component of centrosome and plays a vital role in centriole biogenesis and cell cycle progression control. A total of 31 proteins have been categorized into CEP family protein category and many more are under candidate evaluation. Furthermore, by the recent advancements in genomics and proteomics researches, several new CEP proteins have also been characterized...
October 2013: Protoplasma
Gražvydas Lukinavičius, Darja Lavogina, Meritxell Orpinell, Keitaro Umezawa, Luc Reymond, Nathalie Garin, Pierre Gönczy, Kai Johnsson
The centrosome functions as the main microtubule-organizing center of animal cells and is crucial for several fundamental cellular processes. Abnormalities in centrosome number and composition correlate with tumor progression and other diseases. Although proteomic studies have identified many centrosomal proteins, their interactions are incompletely characterized. The lack of information on the precise localization and interaction partners for many centrosomal proteins precludes comprehensive understanding of centrosome biology...
February 4, 2013: Current Biology: CB
Ambuj Kumar, Rituraj Purohit
Centrosomes are central regulators of mitosis that are often amplified in cancer cells. Centrosomal protein of 63kDa (CEP63) is a centrosomal protein that has an effective role in mitotic spindle assembly and cell cycle regulation. Genetic alterations in CEP63 coding gene has been widely studied for inducing aneuploidy and solid tumors in humans. The nonsynonymous single nucleotide polymorphisms (nsSNPs) are a genetic variant resulting in amino acid substitution and are reported in a wide range of human diseases...
July 15, 2012: Gene
Zhen Zhao, Soohwan Oh, Dapeng Li, Duojiao Ni, Sara Dolatshahi Pirooz, Joo-Hyung Lee, Shunhua Yang, June-Yong Lee, Irene Ghozalli, Vincenzo Costanzo, Jeremy M Stark, Chengyu Liang
Autophagy defects have recently been associated with chromosomal instability, a hallmark of human cancer. However, the functional specificity and mechanism of action of autophagy-related factors in genome stability remain elusive. Here we report that UVRAG, an autophagic tumor suppressor, plays a dual role in chromosomal stability, surprisingly independent of autophagy. We establish that UVRAG promotes DNA double-strand-break repair by directly binding and activating DNA-PK in nonhomologous end joining. Disruption of UVRAG increases genetic instability and sensitivity of cells to irradiation...
May 15, 2012: Developmental Cell
Joo-Hee Sir, Alexis R Barr, Adeline K Nicholas, Ofelia P Carvalho, Maryam Khurshid, Alex Sossick, Stefanie Reichelt, Clive D'Santos, C Geoffrey Woods, Fanni Gergely
Autosomal recessive primary microcephaly (MCPH) is characterized by a substantial reduction in prenatal human brain growth without alteration of the cerebral architecture and is caused by biallelic mutations in genes coding for a subset of centrosomal proteins. Although at least three of these proteins have been implicated in centrosome duplication, the nature of the centrosome dysfunction that underlies the neurodevelopmental defect in MCPH is unclear. Here we report a homozygous MCPH-causing mutation in human CEP63...
November 2011: Nature Genetics
Harald Löffler, Anne Fechter, Marc Matuszewska, Rainer Saffrich, Martin Mistrik, Joachim Marhold, Christin Hornung, Frank Westermann, Jiri Bartek, Alwin Krämer
Centrosomes are central regulators of mitosis that are often amplified in cancer cells. Centrosomes function both as organizers of the mitotic spindle and as reaction centers to trigger activation of Cdk1 and G(2)/M transition in the cell cycle, but their functional organization remains incomplete. Recent proteomic studies have identified novel components of the human centrosome including Cep63, a protein of unknown function that Xenopus studies have implicated in mitotic spindle assembly and spindle inactivation after DNA damage...
March 15, 2011: Cancer Research
Nicola Brown, Vincenzo Costanzo
The DNA damage checkpoint prevents the onset of DNA replication and mitosis when cells are exposed to genotoxic stress. However, it is not clear how cells react to DNA damage, in particular to DNA double strand breaks (DSBs) once they are in mitosis. Using Xenopus laevis egg extract as model system we have uncovered an ATM and ATR dependent checkpoint that targets centrosome dependent spindle assembly in the presence of chromosome breaks. This pathway relies on the phosphorylation by ATM and ATR of a novel centrosomal protein CEP63...
July 1, 2009: Cell Cycle
Eloise Smith, Donniphat Dejsuphong, Alessia Balestrini, Martin Hampel, Christof Lenz, Shunichi Takeda, Alessandro Vindigni, Vincenzo Costanzo
Activation of the protein kinases ATM and ATR following chromosomal breakage prevents initiation of DNA replication and entry into mitosis. However, the effects of ATM and ATR activation in cells already progressing through mitosis are poorly understood. Here we report that ATM and ATR activation induced by DNA double-strand breaks (DSBs) inhibits centrosome-driven spindle assembly in Xenopus laevis mitotic egg extract and somatic cells, delaying mitotic progression. Using a cDNA expression library to screen for ATM and ATR substrates, we identified centrosomal protein CEP63 as an ATM and ATR target required for normal spindle assembly...
March 2009: Nature Cell Biology
Marcilei E Buim, Fernando A Soares, Alvaro S Sarkis, Maria Aparecida Nagai
OBJECTIVE: The aim of the present study was to identify differentially expressed genes that might be associated with the phenotype of superficial and invasive bladder cancer. METHODS: Differential display reverse transcriptase PCR (DDRT-PCR) was used to compare the expression pattern between normal bladder tissue and 4 groups of transitional cell carcinomas of the bladder regarding clinical stage and grade. RESULTS: We were able to identify 72 different transcripts, of which 57 (79%) showed homology to known genes, 12 (17%) to hypothetical proteins and 3 (4%) to human expressed sequence tags...
2005: Oncology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"