scholarly journals Cell cycle-dependent strand bias for UV-induced mutations in the transcribed strand of excision repair-proficient human fibroblasts but not in repair-deficient cells.

1991 ◽  
Vol 11 (4) ◽  
pp. 1927-1934 ◽  
Author(s):  
W G McGregor ◽  
R H Chen ◽  
L Lukash ◽  
V M Maher ◽  
J J McCormick
Keyword(s):  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Uv Light ◽  
Human Fibroblasts ◽  
S Phase ◽  
G1 Phase ◽  
Strand Bias ◽  
Hprt Gene ◽  
Significant Difference ◽  
Nucleotide Excision

To study the effect of nucleotide excision repair on the spectrum of mutations induced in diploid human fibroblasts by UV light (wavelength, 254 nm), we synchronized repair-proficient cells and irradiated them when the HPRT gene was about to be replicated (early S phase) so that there would be no time for repair in that gene before replication, or in G1 phase 6 h prior to S, and determined the kinds and location of mutations in that gene. As a control, we also compared the spectra of mutations induced in synchronized populations of xeroderma pigmentosum cells (XP12BE cells, which are unable to excise UV-induced DNA damage). Among the 84 mutants sequenced, base substitutions predominated. Of the XP mutants from S or G1 and the repair-proficient mutants from S, approximately 62% were G.C----A.T. In the repair-proficient mutants from G1, 47% were. In mutants from the repair-proficient cells irradiated in S, 71% (10 of 14) of the premutagenic lesions were located in the transcribed strand; with mutants from such cells irradiated in G1, only 20% (3 of 15) were. In contrast, there was no statistically significant difference in the fraction of premutagenic lesions located in the transcribed strand of the XP12BE cells; approximately 75% (24 of 32) of the premutagenic lesions were located in that strand, i.e., 15 of 19 (79%) in the S-phase cells and 9 of 13 (69%) in the G1-phase cells. The switch in strand bias supports preferential nucleotide excision repair of UV-induced damage in the transcribed strand of the HPRT gene.

Cell cycle-dependent strand bias for UV-induced mutations in the transcribed strand of excision repair-proficient human fibroblasts but not in repair-deficient cells

1991 ◽  
Vol 11 (4) ◽  
pp. 1927-1934
Author(s):  
W G McGregor ◽  
R H Chen ◽  
L Lukash ◽  
V M Maher ◽  
J J McCormick
Keyword(s):  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Uv Light ◽  
Human Fibroblasts ◽  
S Phase ◽  
G1 Phase ◽  
Strand Bias ◽  
Hprt Gene ◽  
Significant Difference ◽  
Nucleotide Excision

To study the effect of nucleotide excision repair on the spectrum of mutations induced in diploid human fibroblasts by UV light (wavelength, 254 nm), we synchronized repair-proficient cells and irradiated them when the HPRT gene was about to be replicated (early S phase) so that there would be no time for repair in that gene before replication, or in G1 phase 6 h prior to S, and determined the kinds and location of mutations in that gene. As a control, we also compared the spectra of mutations induced in synchronized populations of xeroderma pigmentosum cells (XP12BE cells, which are unable to excise UV-induced DNA damage). Among the 84 mutants sequenced, base substitutions predominated. Of the XP mutants from S or G1 and the repair-proficient mutants from S, approximately 62% were G.C----A.T. In the repair-proficient mutants from G1, 47% were. In mutants from the repair-proficient cells irradiated in S, 71% (10 of 14) of the premutagenic lesions were located in the transcribed strand; with mutants from such cells irradiated in G1, only 20% (3 of 15) were. In contrast, there was no statistically significant difference in the fraction of premutagenic lesions located in the transcribed strand of the XP12BE cells; approximately 75% (24 of 32) of the premutagenic lesions were located in that strand, i.e., 15 of 19 (79%) in the S-phase cells and 9 of 13 (69%) in the G1-phase cells. The switch in strand bias supports preferential nucleotide excision repair of UV-induced damage in the transcribed strand of the HPRT gene.

The DDB2 nucleotide excision repair gene product p48 enhances global genomic repair in p53 deficient human fibroblasts

DNA Repair ◽  
2003 ◽  
Vol 2 (7) ◽  
pp. 819-826 ◽  
Author(s):  
Maureen E. Fitch ◽  
Irina V. Cross ◽  
Stephanie J. Turner ◽  
Shanthi Adimoolam ◽  
Cindy X. Lin ◽  
...  
Keyword(s):  
Gene Product ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Human Fibroblasts ◽  
Repair Gene ◽  
Nucleotide Excision Repair Gene ◽  
Nucleotide Excision

scholarly journals ATR kinase is required for global genomic nucleotide excision repair exclusively during S phase in human cells

2008 ◽  
Vol 105 (46) ◽  
pp. 17896-17901 ◽  
Author(s):  
Yannick Auclair ◽  
Raphael Rouget ◽  
El Bachir Affar ◽  
Elliot A. Drobetsky
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Human Tumor ◽  
Chemotherapeutic Agents ◽  
S Phase ◽  
Cell Cycle Checkpoints ◽  
Lung Fibroblasts ◽  
Nucleotide Excision

Global-genomic nucleotide excision repair (GG-NER) is the only pathway available to humans for removal, from the genome overall, of highly genotoxic helix-distorting DNA adducts generated by many environmental mutagens and certain chemotherapeutic agents, e.g., UV-induced 6–4 photoproducts (6–4PPs) and cyclobutane pyrimidine dimers (CPDs). The ataxia telangiectasia and rad-3-related kinase (ATR) is rapidly activated in response to UV-induced replication stress and proceeds to phosphorylate a plethora of downstream effectors that modulate primarily cell cycle checkpoints but also apoptosis and DNA repair. To investigate whether this critical kinase might participate in the regulation of GG-NER, we developed a novel flow cytometry-based DNA repair assay that allows precise evaluation of GG-NER kinetics as a function of cell cycle. Remarkably, inhibition of ATR signaling in primary human lung fibroblasts by treatment with caffeine, or with siRNA specifically targeting ATR, resulted in total inhibition of 6–4PP removal during S phase, whereas cells repaired normally during either G0/G1 or G2/M. Similarly striking S-phase-specific defects in GG-NER of both 6–4PPs and CPDs were documented in ATR-deficient Seckel syndrome skin fibroblasts. Finally, among six diverse model human tumor strains investigated, three manifested complete abrogation of 6–4PP repair exclusively in S-phase populations. Our data reveal a highly novel role for ATR in the regulation of GG-NER uniquely during S phase of the cell cycle, and indicate that many human cancers may be characterized by a defect in this regulation.

scholarly journals Mutations in Replicative Stress Response Pathways Are Associated with S Phase-specific Defects in Nucleotide Excision Repair

2015 ◽  
Vol 291 (2) ◽  
pp. 522-537 ◽  
Author(s):  
François Bélanger ◽  
Jean-Philippe Angers ◽  
Émile Fortier ◽  
Ian Hammond-Martel ◽  
Santiago Costantino ◽  
...  
Keyword(s):  
Stress Response ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
S Phase ◽  
Replicative Stress ◽  
Nucleotide Excision

scholarly journals Effect of nucleotide excision repair on hprt gene mutations in rodent cells exposed to DNA ethylating agents

Mutagenesis ◽  
1997 ◽  
Vol 12 (6) ◽  
pp. 417-424 ◽  
Author(s):  
Christel W.Op het Veld ◽  
Sandrine van Hees-Stuivenberg ◽  
Albert A. van Zeeland ◽  
Jacob G Jansen
Keyword(s):  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Gene Mutations ◽  
Hprt Gene ◽  
Nucleotide Excision

scholarly journals Characterization of G1 checkpoint control in the yeast Saccharomyces cerevisiae following exposure to DNA-damaging agents.

Genetics ◽  
1994 ◽  
Vol 138 (2) ◽  
pp. 271-281 ◽  
Author(s):  
W Siede ◽  
A S Friedberg ◽  
I Dianova ◽  
E C Friedberg
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
S Phase ◽  
Checkpoint Control ◽  
Cycle Arrest ◽  
Dna Damaging Agents ◽  
Nucleotide Excision ◽  
G1 Checkpoint

Abstract The delay of S-phase following treatment of yeast cells with DNA-damaging agents is an actively regulated response that requires functional RAD9 and RAD24 genes. An analysis of cell cycle arrest indicates the existence of (at least) two checkpoints for damaged DNA prior to S-phase; one at START (a G1 checkpoint characterized by pheromone sensitivity of arrested cells) and one between the CDC4- and CDC7-mediated steps (termed the G1/S checkpoint). When a dna1-1 mutant (that affects early events of replicon initiation) also carries a rad9 deletion mutation, it manifests a failure to arrest in G1/S following incubation at the restrictive temperature. This failure to execute regulated G1/S arrest is correlated with enhanced thermosensitivity of colony-forming ability. In an attempt to characterize the signal for RAD9 gene-dependent G1 and G1/S cell cycle arrest, we examined the influence of the continued presence of unexcised photoproducts. In mutants defective in nucleotide excision repair, cessation of S-phase was observed at much lower doses of UV radiation compared to excision-proficient cells. However, this response was not RAD9-dependent. We suggest that an intermediate of nucleotide excision repair, such as DNA strand breaks or single-stranded DNA tracts, is required to activate RAD9-dependent G1 and G1/S checkpoint controls.

Clustered Sites of DNA Repair Synthesis during Early Nucleotide Excision Repair in Ultraviolet Light-Irradiated Quiescent Human Fibroblasts

2002 ◽  
Vol 276 (2) ◽  
pp. 284-295 ◽  
Author(s):  
Maria Svetlova ◽  
Lioudmila Solovjeva ◽  
Nadezhda Pleskach ◽  
Natalia Yartseva ◽  
Tatyana Yakovleva ◽  
...  
Keyword(s):  
Dna Repair ◽  
Nucleotide Excision Repair ◽  
Ultraviolet Light ◽  
Excision Repair ◽  
Human Fibroblasts ◽  
Repair Synthesis ◽  
Nucleotide Excision ◽  
Dna Repair Synthesis
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