The Cytoskeleton Protein Filamin-A Is Required for an Efficient Recombinational DNA Double Strand Break Repair

Yue, Jingyin; Wang, Qin; Lu, Huimei; Brenneman, Mark A.; Fan, Feiyue; Shen, Zhiyuan

doi:10.1158/0008-5472.can-09-2177

Cited by 60 publications

(83 citation statements)

References 44 publications

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“…This finding is particularly important because Ku proteins are involved in DSB repair by NHEJ, and inactivation of Ku proteins leads to defects in telomere maintenance and chromosomal end fusion (24). Our IP/MS experiments also indicate that TCTP interacts with filamin A, which appears to be required for efficient HRR (25). The role of TCTP in such critical mechanisms that maintain genomic integrity may explain in part why homozygous mutation in TCTP is embryonically lethal (2).…”

Section: Discussionmentioning

confidence: 59%

Role of the translationally controlled tumor protein in DNA damage sensing and repair

Zhang

Toledo²,

Pandey³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The translationally controlled tumor protein (TCTP) is essential for survival by mechanisms that as yet are incompletely defined. Here we describe an important role of TCTP in response to DNA damage. Upon exposure of normal human cells to low-dose γ rays, the TCTP protein level was greatly increased, with a significant enrichment in nuclei. TCTP up-regulation occurred in a manner dependent on ataxia-telangiectasia mutated (ATM) kinase and the DNA-dependent protein kinase and was associated with protective effects against DNA damage. In chromatin of irradiated cells, coimmunoprecipitation experiments showed that TCTP forms a complex with ATM and γH2A.X, in agreement with its distinct localization with the foci of the DNA damage-marker proteins γH2A.X, 53BP1, and P-ATM. In cells lacking TCTP, repair of chromosomal damage induced by γ rays was compromised significantly. TCTP also was shown to interact with p53 and the DNA-binding subunits, Ku70 and Ku80, of DNA-dependent protein kinase. TCTP knockdown led to decreased levels of Ku70 and Ku80 in nuclei of irradiated cells and attenuated their DNA-binding activity. It also attenuated the radiation-induced G 1 delay but prolonged the G 2 delay. TCTP therefore may play a critical role in maintaining genomic integrity in response to DNA-damaging agents.low dose ionizing radiation | adaptive responses | DNA repair | cell cycle checkpoints | genomic stability

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Section: Discussionmentioning

confidence: 59%

Role of the translationally controlled tumor protein in DNA damage sensing and repair

Zhang

Toledo²,

Pandey³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Filamin A has been implicated in cell motility, adhesion and invasion . However, novel functions of filamin A have recently been described within the cell nucleus, such as the regulation of nuclear shape during EMT and of DNA double-strand break repair (Yue et al 2009, Gay et al 2011.…”

Section: 25(oh) 2 D 3 Is a Pleiotropic Hormonementioning

confidence: 99%

Vitamin D and colon cancer

Перейра¹,

Larriba²,

Múñoz³

2012

Endocrine-Related Cancer

110

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The most active vitamin D metabolite, 1α,25-dihydroxyvitamin D3(1,25(OH)2D3), is a pleiotropic hormone with wide regulatory actions. Classically, vitamin D deficiency was known to alter calcium and phosphate metabolism and bone biology. In addition, recent epidemiological and experimental studies support the association of vitamin D deficiency with a large variety of human diseases, and particularly with the high risk of colorectal cancer. By regulating the expression of many genes via several mechanisms, 1,25(OH)2D3induces differentiation, controls the detoxification metabolism and cell phenotype, sensitises cells to apoptosis and inhibits the proliferation of cultured human colon carcinoma cells. Consistently, 1,25(OH)2D3and several of its analogues decrease intestinal tumourigenesis in animal models. Molecular, genetic and clinical data in humans are scarce but they suggest that vitamin D is protective against colon cancer. Clearly, the available evidence warrants new, well-designed, large-scale trials to clarify the role of vitamin D in the prevention and/or therapy of this important neoplasia.

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“…Therefore, the presence of MN or NPB could indirectly reflect the cell DNA repair capacity [8]. In fact, increased frequencies of spontaneous and mutagen induced MN or NPBs have been observed in different cells deficient in DNA repair mechanisms such as non-homologous DNA end-joining [10] or homologous recombination [11,12].…”

Section: Introductionmentioning

confidence: 99%

Ionizing radiation or mitomycin-induced micronuclei in lymphocytes of BRCA1 or BRCA2 mutation carriers

Gutiérrez‐Enríquez

Cajal

Alonso

et al. 2010

Breast Cancer Res Treat

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BRCA1 and BRCA2 genes are essential in preserving the integrity of genome, and it is not unambiguously clear whether the heterozygosity status may affect BRCA1 or BRCA2 functions. This may have implications for the clinical management of BRCA1 and BRCA2 mutation carriers both in breast cancer (BC) screening modality and in cancer treatment based on DNA-damaging or DNA-repair-inhibiting drugs. We investigated whether lymphocytes carrying BRCA1 or BRCA2 mutations displayed an increased sensitivity to radiation or mitomycin C (MMC) in vitro treatments. Peripheral blood from 21 BRCA1 mutation carriers (12 with BC and 9 healthy), 24 BRCA2 carriers (13 with BC and 11 healthy), 15 familial BC patients without detected mutation in BRCA1 or BRCA2 and 16 controls without familial history of cancer (5 with BC and 11 healthy) were irradiated or treated with MMC. Chromosomal damage was measured using the cytokinesis-block micronucleus assay. We evaluated micronuclei (MN) and nucleoplasmic bridges (NPBs). The BRCA2 mutation carriers and familial BC patients without detected mutation in BRCA1 or BRCA2 showed less basal NPB than BRCA1 carriers and controls. The BRCA1 (+/-) or BRCA2 (+/-) lymphocytes did not have increased frequencies of MN or NPB after irradiation. In contrast, BRCA2 (+/-) lymphocytes presented higher levels of MN after MMC exposure than BRCA1 carriers and controls. The monoallelic BRCA1 or BRCA2 pathogenic mutations seem not to be associated with an enhanced radiosensitivity. The mutation of one BRCA2 allele conferred an increased sensitivity to MMC, presumably because of the role of this gene in the repair of MMC-induced DNA damage. This finding indicates that the MMC-induced MN analysis could be useful in identifying functional deficiencies of BRCA2 or genes related to BRCA2. Since MMC can be used as an anti-cancer drug, these data may be relevant for the management and follow-up of BRCA2 mutation carriers.

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The Cytoskeleton Protein Filamin-A Is Required for an Efficient Recombinational DNA Double Strand Break Repair

Cited by 60 publications

References 44 publications

Role of the translationally controlled tumor protein in DNA damage sensing and repair

Role of the translationally controlled tumor protein in DNA damage sensing and repair

Vitamin D and colon cancer

Ionizing radiation or mitomycin-induced micronuclei in lymphocytes of BRCA1 or BRCA2 mutation carriers

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