CEP152 是一种在 Seckel 综合征中被破坏的基因组维护蛋白。
CEP152 is a genome maintenance protein disrupted in Seckel syndrome.
机构信息
Department of Medical Biology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey.
出版信息
Nat Genet. 2011 Jan;43(1):23-6. doi: 10.1038/ng.725. Epub 2010 Dec 5.
Abstract
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.
摘要
功能损伤的 DNA 损伤反应通路会导致基因组不稳定性增加。本文中，我们将中心体蛋白 CEP152 描述为基因组完整性和细胞对 DNA 损伤反应的新调节因子。通过纯合性作图和外显子组测序，我们在 Seckel 综合征中鉴定出 CEP152 突变，并证实功能受损的 CEP152 通过增强 ATM 信号的激活和增加 H2AX 磷酸化，导致复制压力下基因组缺陷的积累。
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本文引用的文献
1
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Am J Hum Genet. 2010 Jul 9;87(1):40-51. doi: 10.1016/j.ajhg.2010.06.003.
2
Functional genomic screens identify CINP as a genome maintenance protein.
Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19304-9. doi: 10.1073/pnas.0909345106. Epub 2009 Nov 4.
3
A mouse model of ATR-Seckel shows embryonic replicative stress and accelerated aging.
Nat Genet. 2009 Aug;41(8):891-8. doi: 10.1038/ng.420. Epub 2009 Jul 20.
4
GammaH2AX and cancer.
Nat Rev Cancer. 2008 Dec;8(12):957-67. doi: 10.1038/nrc2523. Epub 2008 Nov 13.
5
Drosophila asterless and vertebrate Cep152 Are orthologs essential for centriole duplication.
Genetics. 2008 Dec;180(4):2081-94. doi: 10.1534/genetics.108.095141. Epub 2008 Oct 14.
6
ATR: an essential regulator of genome integrity.
Nat Rev Mol Cell Biol. 2008 Aug;9(8):616-27. doi: 10.1038/nrm2450. Epub 2008 Jul 2.
7
Mutations in the pericentrin (PCNT) gene cause primordial dwarfism.
Science. 2008 Feb 8;319(5864):816-9. doi: 10.1126/science.1151174. Epub 2008 Jan 3.
8
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Nat Genet. 2008 Feb;40(2):232-6. doi: 10.1038/ng.2007.80. Epub 2007 Dec 23.
9
H2AX phosphorylation within the G1 phase after UV irradiation depends on nucleotide excision repair and not DNA double-strand breaks.
Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9891-6. doi: 10.1073/pnas.0603779103. Epub 2006 Jun 20.
10
Proteomic characterization of the human centrosome by protein correlation profiling.
Nature. 2003 Dec 4;426(6966):570-4. doi: 10.1038/nature02166.
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