scholarly journals Repair protein persistence at DNA lesions characterizes XPF defect with Cockayne syndrome features

2018 ◽  
Vol 46 (18) ◽  
pp. 9563-9577 ◽  
Author(s):  
Mariangela Sabatella ◽  
Arjan F Theil ◽  
Cristina Ribeiro-Silva ◽  
Jana Slyskova ◽  
Karen Thijssen ◽  
...  
Keyword(s):  
Cockayne Syndrome ◽  
Dna Lesions ◽  
Repair Protein

scholarly journals The Cockayne syndrome protein B is involved in the repair of 5-AZA-2′-deoxycytidine-induced DNA lesions

Oncotarget ◽  
2018 ◽  
Vol 9 (80) ◽  
pp. 35069-35084 ◽  
Author(s):  
Estefanía Burgos-Morón ◽  
José Manuel Calderón-Montaño ◽  
Nuria Pastor ◽  
Andreas Höglund ◽  
Ángel Ruiz-Castizo ◽  
...  
Keyword(s):  
Cockayne Syndrome ◽  
Dna Lesions ◽  
Syndrome Protein ◽  
Protein B

scholarly journals Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1671 ◽  
Author(s):  
Marios G. Krokidis ◽  
Mariarosaria D’Errico ◽  
Barbara Pascucci ◽  
Eleonora Parlanti ◽  
Annalisa Masi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Excision Repair ◽  
Enzymatic Digestion ◽  
Cockayne Syndrome ◽  
Dna Lesions ◽  
Premature Aging ◽  
Neurological Features ◽  
Oxygen Tensions ◽  
Base Excision

Cockayne Syndrome (CS) is an autosomal recessive neurodegenerative premature aging disorder associated with defects in nucleotide excision repair (NER). Cells from CS patients, with mutations in CSA or CSB genes, present elevated levels of reactive oxygen species (ROS) and are defective in the repair of a variety of oxidatively generated DNA lesions. In this study, six purine lesions were ascertained in wild type (wt) CSA, defective CSA, wtCSB and defective CSB-transformed fibroblasts under different oxygen tensions (hyperoxic 21%, physioxic 5% and hypoxic 1%). In particular, the four 5′,8-cyclopurine (cPu) and the two 8-oxo-purine (8-oxo-Pu) lesions were accurately quantified by LC-MS/MS analysis using isotopomeric internal standards after an enzymatic digestion procedure. cPu levels were found comparable to 8-oxo-Pu in all cases (3–6 lesions/106 nucleotides), slightly increasing on going from hyperoxia to physioxia to hypoxia. Moreover, higher levels of four cPu were observed under hypoxia in both CSA and CSB-defective cells as compared to normal counterparts, along with a significant enhancement of 8-oxo-Pu. These findings revealed that exposure to different oxygen tensions induced oxidative DNA damage in CS cells, repairable by NER or base excision repair (BER) pathways. In NER-defective CS patients, these results support the hypothesis that the clinical neurological features might be connected to the accumulation of cPu. Moreover, the elimination of dysfunctional mitochondria in CS cells is associated with a reduction in the oxidative DNA damage.

scholarly journals The retinoblastoma homolog RBR 1 mediates localization of the repair protein RAD 51 to DNA lesions in Arabidopsis

2017 ◽  
Vol 36 (9) ◽  
pp. 1279-1297 ◽  
Author(s):  
Sascha Biedermann ◽  
Hirofumi Harashima ◽  
Poyu Chen ◽  
Maren Heese ◽  
Daniel Bouyer ◽  
...  
Keyword(s):  
Dna Lesions ◽  
Repair Protein

scholarly journals Biochemical and Biological Characterization of Wild-type and ATPase-deficient Cockayne Syndrome B Repair Protein

1998 ◽  
Vol 273 (19) ◽  
pp. 11844-11851 ◽  
Author(s):  
Elisabetta Citterio ◽  
Suzanne Rademakers ◽  
Gijsbertus T. J. van der Horst ◽  
Alain J. van Gool ◽  
Jan H.J. Hoeijmakers ◽  
...  
Keyword(s):  
Cockayne Syndrome ◽  
Biological Characterization ◽  
Wild Type ◽  
Repair Protein

scholarly journals Disruption of the Cockayne Syndrome B Gene Impairs Spontaneous Tumorigenesis in Cancer-Predisposed Ink4a/ARF Knockout Mice

2001 ◽  
Vol 21 (5) ◽  
pp. 1810-1818 ◽  
Author(s):  
Yi Lu ◽  
Hanzhou Lian ◽  
Prerna Sharma ◽  
Nicole Schreiber-Agus ◽  
Robert G. Russell ◽  
...  
Keyword(s):  
Dna Repair ◽  
Colony Formation ◽  
Gene Disruption ◽  
Formation Rate ◽  
Cockayne Syndrome ◽  
Dna Lesions ◽  
Synthesis Rate ◽  
Mrna Synthesis ◽  
Antineoplastic Effect ◽  
Repair Defect

ABSTRACT Cells isolated from individuals with Cockayne syndrome (CS) have a defect in transcription-coupled DNA repair, which rapidly corrects certain DNA lesions located on the transcribed strand of active genes. Despite this DNA repair defect, individuals with CS group A (CSA) or group B (CSB) do not exhibit an increased spontaneous or UV-induced cancer rate. In order to investigate the effect of CSB deficiency on spontaneous carcinogenesis, we crossed CSB−/− mice with cancer-prone mice lacking the p16Ink4a/p19ARFtumor suppressor locus. CSB−/− mice are sensitive to UV-induced skin cancer but show no increased rate of spontaneous cancer. CSB−/− Ink4a/ARF−/− mice developed 60% fewer tumors than Ink4a/ARF−/− animals and demonstrated a longer tumor-free latency time (260 versus 150 days). Moreover, CSB−/− Ink4a/ARF−/− mouse embryo fibroblasts (MEFs) exhibited a lower colony formation rate after low-density seeding, a lower rate of H-Ras-induced transformation, slower proliferation, and a lower mRNA synthesis rate than Ink4a/ARF−/− MEFs. CSB−/−Ink4a/ARF−/− MEFs were also more sensitive to UV-induced p53 induction and UV-induced apoptosis than were Ink4a/ARF−/− MEFs. In order to investigate whether the apparent antineoplastic effect of CSB gene disruption was caused by sensitization to genotoxin-induced (p53-mediated) apoptosis or by p53-independent sequelae, we also generated p53−/− and CSB−/− p53−/− MEFs. The CSB−/− p53−/− MEFs demonstrated lower colony formation efficiency, a lower proliferation rate, a lower mRNA synthesis rate, and a higher rate of UV-induced cell death than p53−/− MEFs. Collectively, these results indicate that the antineoplastic effect of CSB gene disruption is at least partially p53 independent; it may result from impaired transcription or from apoptosis secondary to environmental or endogenous DNA damage.

The Cockayne syndrome group B DNA repair protein as an anti-cancer target

2001 ◽  
Author(s):  
Y. Lu ◽  
Sridhar Mani ◽  
Ekambar Kandimalla ◽  
Dong Yu ◽  
Sudhir Agrawal ◽  
...  
Keyword(s):  
Dna Repair ◽  
Cockayne Syndrome ◽  
Repair Protein ◽  
Anti Cancer ◽  
Dna Repair Protein ◽  
Group B

Distinct kinetics of DNA repair protein accumulation at DNA lesions and cell cycle-dependent formation of γH2AX- and NBS1-positive repair foci

2015 ◽  
Vol 107 (12) ◽  
pp. 440-454 ◽  
Author(s):  
Jana Suchánková ◽  
Stanislav Kozubek ◽  
Soňa Legartová ◽  
Petra Sehnalová ◽  
Thomas Küntziger ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Dna Lesions ◽  
Protein Accumulation ◽  
Repair Protein ◽  
Dna Repair Protein ◽  
Cycle Dependent ◽  
Kinetics Of

scholarly journals Cooperation of the Cockayne Syndrome Group B Protein and Poly(ADP-Ribose) Polymerase 1 in the Response to Oxidative Stress

2005 ◽  
Vol 25 (17) ◽  
pp. 7625-7636 ◽  
Author(s):  
Tina Thorslund ◽  
Cayetano von Kobbe ◽  
Jeanine A. Harrigan ◽  
Fred E. Indig ◽  
Mette Christiansen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cellular Response ◽  
Genetic Disorder ◽  
Cockayne Syndrome ◽  
Dna Lesions ◽  
Dna Breaks ◽  
Group B ◽  
Parp 1

ABSTRACT Cockayne syndrome (CS) is a rare genetic disorder characterized as a segmental premature-aging syndrome. The CS group B (CSB) protein has previously been implicated in transcription-coupled repair, transcriptional elongation, and restoration of RNA synthesis after DNA damage. Recently, evidence for a role of CSB in base excision repair of oxidative DNA lesions has accumulated. In our search to understand the molecular function of CSB in this process, we identify a physical and functional interaction between CSB and poly(ADP-ribose) polymerase-1 (PARP-1). PARP-1 is a nuclear enzyme that protects the integrity of the genome by responding to oxidative DNA damage and facilitating DNA repair. PARP-1 binds to single-strand DNA breaks which activate the catalytic ability of PARP-1 to add polymers of ADP-ribose to various proteins. We find that CSB is present at sites of activated PARP-1 after oxidative stress, identify CSB as a new substrate of PARP-1, and demonstrate that poly(ADP-ribosyl)ation of CSB inhibits its DNA-dependent ATPase activity. Furthermore, we find that CSB-deficient cell lines are hypersensitive to inhibition of PARP. Our results implicate CSB in the PARP-1 poly(ADP-ribosyl)ation response after oxidative stress and thus suggest a novel role of CSB in the cellular response to oxidative damage.

scholarly journals DNA damage stabilizes interaction of CSB with the transcription elongation machinery

2004 ◽  
Vol 166 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Vincent van den Boom ◽  
Elisabetta Citterio ◽  
Deborah Hoogstraten ◽  
Angelika Zotter ◽  
Jean-Marc Egly ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Dna Damage ◽  
Dna Repair ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
High Molecular Weight ◽  
Transcription Elongation ◽  
Cockayne Syndrome ◽  
Dna Lesions ◽  
High Molecular Weight Complex

The Cockayne syndrome B (CSB) protein is essential for transcription-coupled DNA repair (TCR), which is dependent on RNA polymerase II elongation. TCR is required to quickly remove the cytotoxic transcription-blocking DNA lesions. Functional GFP-tagged CSB, expressed at physiological levels, was homogeneously dispersed throughout the nucleoplasm in addition to bright nuclear foci and nucleolar accumulation. Photobleaching studies showed that GFP-CSB, as part of a high molecular weight complex, transiently interacts with the transcription machinery. Upon (DNA damage-induced) transcription arrest CSB binding these interactions are prolonged, most likely reflecting actual engagement of CSB in TCR. These findings are consistent with a model in which CSB monitors progression of transcription by regularly probing elongation complexes and becomes more tightly associated to these complexes when TCR is active.

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