RAS Transformation Requires CUX1-Dependent Repair of Oxidative DNA Damage

Ramdzan, Zubaidah M.; Vadnais, Charles; Pal, Ranjana; Vandal, Guillaume; Cadieux, C. Linn; Leduy, Lam; Davoudi, Sayeh; Hulea, Laura; Yao, Lu; Karnezis, Anthony N.; Paquet, Marilène; Dankort, David; Nepveu, Alain

doi:10.1371/journal.pbio.1001807

Cited by 56 publications

(122 citation statements)

References 103 publications

(142 reference statements)

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“…Lentiviruses expressing CUX2 fragments (CR1CR2, CR2CR3HD, CR3HD, and lacZ) and short hairpin RNA against rat Cux2 (MISSION shRNA pLKO.1, Sigma) and human CUX2 (The RNAi Consortium) were produced as described previously (53). Protein expression levels of endogenous CUX2 were determined using anti-CUX2-356 antibody (67), whereas recombinant CUX2 proteins were detected using anti-HA (MMS-101R, Covance).…”

Section: Methodsmentioning

confidence: 99%

“…Indeed, higher CUX1 expression prevents RAS-induced senescence and promotes the development of tumors from cells that spontaneously acquire an activating Kras mutation (53). Conversely, CUX1 knockdown is synthetic lethal to KRAS-transformed cells (53,54). Together, these findings illustrated a case of non-oncogene addiction whereby cancer cells have become acutely dependent on the heightened expression and activity of a protein that is not itself an oncogene (55,56).…”

Section: Reactive Oxygen Species (Ros)mentioning

confidence: 98%

“…Cut repeats were originally characterized as domains that bind to DNA in cooperation with one another or with the Cut homeodomain (50,51). More recently, Cut repeats of CUX1 were shown to bind to OGG1 and stimulate both its glycosylase and AP lyase enzymatic activities (52,53). Knockdown or genetic inactivation of CUX1 was found to delay the repair of oxidative DNA damage, whereas higher CUX1 expression accelerated DNA repair.…”

Section: Reactive Oxygen Species (Ros)mentioning

confidence: 99%

“…In cancer, however, this biochemical activity is exploited by RAS-driven tumor cells that generate high levels of ROS. Indeed, higher CUX1 expression prevents RAS-induced senescence and promotes the development of tumors from cells that spontaneously acquire an activating Kras mutation (53). Conversely, CUX1 knockdown is synthetic lethal to KRAS-transformed cells (53,54).…”

Section: Reactive Oxygen Species (Ros)mentioning

confidence: 99%

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CUX2 Protein Functions as an Accessory Factor in the Repair of Oxidative DNA Damage

Pal

Ramdzan

Kaur

et al. 2015

Journal of Biological Chemistry

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Background: CUX2 contains three Cut repeat domains and is expressed in postmitotic neurons. Results: Cut repeats stimulate the OGG1 DNA glycosylase, and lower or higher CUX2 expression, respectively, delays or accelerates repair of oxidative DNA damage. Conclusion: CUX2 functions as an accessory factor in base excision repair. Significance: CUX2 contributes to the maintenance of genome integrity in long lived neurons.

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Section: Methodsmentioning

confidence: 99%

Section: Reactive Oxygen Species (Ros)mentioning

confidence: 98%

Section: Reactive Oxygen Species (Ros)mentioning

confidence: 99%

Section: Reactive Oxygen Species (Ros)mentioning

confidence: 99%

See 2 more Smart Citations

CUX2 Protein Functions as an Accessory Factor in the Repair of Oxidative DNA Damage

Pal

Ramdzan

Kaur

et al. 2015

Journal of Biological Chemistry

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“…CUX1 gene encodes a homeodomain protein that has both oncogene (cell cycle progression, cell migration and repair of DNA damages) and tumor suppressor gene (TSG) (repression of PI3K-AKT pathway and base excision repair) activities [1,2,3,4,5]. Loss of heterozygosity (LOH) at 7q22.1 where CUX1 resides is common in many cancers [1].…”

Section: Introductionmentioning

confidence: 99%

Intratumoral heterogeneity for inactivating frameshift mutation of CUX1 and SIRT1 genes in gastric and colorectal cancers

Jo¹,

Kim²,

Yoo³

et al. 2017

pjp

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*These two authors contributed equally to this work.Both CUX1 and SIRT1 are considered tumor suppressor genes (TSGs), but it is not known whether CUX1 and SIRT1 alterations are different between high microsatellite instability (MSI-H) and microsatellite stable MSI (MSS) cancers. We identified frameshift mutations of CUX1 in 4 cases of colorectal cancer (CRC) and of SIRT1 in 1 case of gastric cancer (GC) and 3 cases of CRC. All of them were found in GC or CRC with MSI-H (3.5% of MSI-H for each gene), but neither in GC nor CRC with MSS. In addition, we analyzed intratumoral heterogeneity (ITH) of the CUX1 frameshift mutation and found that two CRCs (12.5%) harbored regional ITH of the frameshift mutation. Our data indicate that there exist frameshift mutations of CUX1 and SIRT1 genes as well as ITH of CUX1 frameshift mutation in MSI-H cancers, which together might play a role in tumorigenesis of GC and CRC with MSI-H.

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Exploiting human and mouse transcriptomic data: Identification of circadian genes and pathways influencing health

et al. 2015

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The power of the application of bioinformatics across multiple publicly available transcriptomic data sets was explored. Using 19 human and mouse circadian transcriptomic data sets, we found that NR1D1 and NR1D2 which encode heme‐responsive nuclear receptors are the most rhythmic transcripts across sleep conditions and tissues suggesting that they are at the core of circadian rhythm generation. Analyzes of human transcriptomic data show that a core set of transcripts related to processes including immune function, glucocorticoid signalling, and lipid metabolism is rhythmically expressed independently of the sleep‐wake cycle. We also identify key transcripts associated with transcription and translation that are disrupted by sleep manipulations, and through network analysis identify putative mechanisms underlying the adverse health outcomes associated with sleep disruption, such as diabetes and cancer. Comparative bioinformatics applied to existing and future data sets will be a powerful tool for the identification of core circadian‐ and sleep‐dependent molecules.

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RAS Transformation Requires CUX1-Dependent Repair of Oxidative DNA Damage

Abstract: The base excision repair (BER) that repairs oxidative damage is upregulated as an adaptive response in maintaining tumorigenesis of RAS-transformed cancer cells.

Cited by 56 publications

References 103 publications

CUX2 Protein Functions as an Accessory Factor in the Repair of Oxidative DNA Damage

CUX2 Protein Functions as an Accessory Factor in the Repair of Oxidative DNA Damage

Intratumoral heterogeneity for inactivating frameshift mutation of CUX1 and SIRT1 genes in gastric and colorectal cancers

Exploiting human and mouse transcriptomic data: Identification of circadian genes and pathways influencing health

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