DNA repair efficiency in transgenic mice over expressing ribosomal protein S3

Hegde, Vijay; Yadavilli, Sridevi; McLaughlin, Leslie D.; Deutsch, Walter

doi:10.1016/j.mrfmmm.2009.03.005

Cited by 14 publications

(18 citation statements)

References 24 publications

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“…RPS3 overexpressing transgenic [13] and wild type C57BL6 mice were maintained on a 12 h light/dark cycle and were fed a standard mouse lab chow and water ad libitum. 15-month and 4-month old transgenic and wild-type male mice were sacrificed by CO 2 asphyxiation and cervical dislocation.…”

Section: Animalsmentioning

confidence: 99%

“…Total protein from tissues was extracted as previously described [13] and protein concentration determined by Bradford assay [18]. Western blot analysis was performed by resolving the total protein from tissues by SDS-PAGE and transferred onto nitrocellulose membrane by electro transfer technique.…”

Section: Detection Of Protein Expression By Western Blot Analysismentioning

confidence: 99%

“…Captured images were processed using ImageJ software. Expression intensity was determined as previously described [13], where the microscope parameters where set for control tissue (wild-type) and the transgenic tissue slides were viewed at the same setting.…”

Section: Detection Of Rps3 and 8-oxodg For Expression And Colocalizatmentioning

confidence: 99%

“…We have previously reported that over expression of RPS3 in oxidatively stressed MEFs results in increase in DNA damage that involves the nuclear translocation of RPS3 to sites of 8-oxodG and the likely blocking of DNA repair at this lesion [13]. We hypothesized that a block to repair of 8-oxodG due to RPS3 over expression will lead to accumulation of spontaneously occurring endogenous oxidative DNA damage as animals age.…”

Section: Effect Of Rps3 Over Expression On Age-dependent Dna Damage Amentioning

confidence: 99%

“…Mouse embryonic fibroblasts (MEFs) isolated from transgenic mice over expressing RPS3 showed translocation of RPS3 from the cytoplasm to the nucleus and colocalization to 8-oxodG foci. Cells exposed to oxidative stress also showed increased accumulation of DNA damage when compared to MEFs from wild-type mice [13]. However, little is known about the role of RPS3 in inducing tumors due to age dependent accumulation of spontaneous DNA damage.…”

Section: Introductionmentioning

confidence: 99%

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Age Dependent Accumulation of Spontaneous DNA Damage in Liver of Transgenic Mice over Expressing Ribosomal Protein S3

Hegde¹,

Yadavilli²,

Deutsch³

2016

Mol Biol

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Oxidative stress has been associated with the aging process and increased cancer incidence mainly due to accumulation of free radical dependent cellular damage. Reactive oxygen species (ROS) induced formation of 7,8-dihydro-8-oxoguanine (8-oxodG) has the potential to mispair with Adenine during DNA replication in key genes involved in the development of cancer. Human ribosomal protein S3 (RPS3) participates in a variety of reactions beyond its role in protein synthesis, such as processing of oxidative DNA damage. We have shown ex vivo that oxidative stress causes RPS3 to translocate to the nucleus, bind to sites of 8-oxodG with an extraordinarily high binding affinity and interferes with 8-oxodG repair in vitro. Furthermore, our in vivo studies using RPS3 over expressing transgenic mice showed translocation of RPS3 to the nucleus in mouse embryonic fibroblasts (MEFs) and co-localization to 8-oxodG foci with an increase in DNA damage. In this study, we show age dependent accumulation of DNA damage (double strand breaks [DSBs] and fragmented DNA) in aging (15-month old) transgenic mice over expressing RPS3. We also observed increase in DNA damage particularly 8-oxodG, in the liver of older transgenic mice which showed a pre-neoplastic pathology and presence of hepatic tumors. The older transgenic livers had significantly higher p53 expression compared to age matched wild-type mice. These results provide evidence for role of RPS3 over expression interfering with DNA repair and predisposing animals to carcinogenesis but also underscore the role of RPS3 expression plays in the DNA damage signaling pathway and in maintenance of genome integrity by channeling cells either towards cell survival (DNA repair) or cell death (apoptosis).

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Section: Animalsmentioning

confidence: 99%

Section: Detection Of Protein Expression By Western Blot Analysismentioning

confidence: 99%

Section: Detection Of Rps3 and 8-oxodg For Expression And Colocalizatmentioning

confidence: 99%

Section: Effect Of Rps3 Over Expression On Age-dependent Dna Damage Amentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Age Dependent Accumulation of Spontaneous DNA Damage in Liver of Transgenic Mice over Expressing Ribosomal Protein S3

Hegde¹,

Yadavilli²,

Deutsch³

2016

Mol Biol

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Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role in mitochondrial DNA damage surveillance

Kim

2013

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Ribosomal protein S3 (rpS3) is known to play critical roles in ribosome biogenesis and DNA repair. When cellular ROS levels increase, the mitochondrial genes are highly vulnerable to DNA damage. Increased ROS induces rpS3 accumulation in the mitochondria for DNA repair while significantly decreasing the cellular protein synthesis. For the entrance into the mitochondria, the accumulation of rpS3 was regulated by interaction with HSP90, HSP70, and TOM70. Pretreatment with geldanamycin, which binds to the ATP pocket of HSP90, significantly decreased the interaction of rpS3 with HSP90 and stimulated the accumulation of rpS3 in the mitochondria. Furthermore, cellular ROS was decreased and mtDNA damage was rescued when levels of rpS3 were increased in the mitochondria. Therefore, we concluded that when mitochondrial DNA damages accumulate due to increased levels of ROS, rpS3 accumulates in the mitochondria to repair damaged DNA due to the decreased interaction between rpS3 and HSP90 in the cytosol.

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Eukaryotic ribosomal protein S3: A constituent of translational machinery and an extraribosomal player in various cellular processes

et al. 2014

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DNA repair efficiency in transgenic mice over expressing ribosomal protein S3

Cited by 14 publications

References 24 publications

Age Dependent Accumulation of Spontaneous DNA Damage in Liver of Transgenic Mice over Expressing Ribosomal Protein S3

Age Dependent Accumulation of Spontaneous DNA Damage in Liver of Transgenic Mice over Expressing Ribosomal Protein S3

Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role in mitochondrial DNA damage surveillance

Eukaryotic ribosomal protein S3: A constituent of translational machinery and an extraribosomal player in various cellular processes

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