Normal telomere length and chromosomal end capping in poly(ADP-ribose) polymerase–deficient mice and primary cells despite increased chromosomal instability
Enrique Samper,Fermín A. Goytisolo,Josiane Ménissier-de Murcia,Eva González-Suárez,Juan C. Cigudosa,Gilbert de Murcia,Maria A. Blasco +6 more
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The results presented here indicate that PARp-1 does not play a major role in regulating telomere length or in telomeric end capping, and the chromosomal instability of PARP-1−/− primary cells can be explained by the repair defect associated to PARP -1 deficiency.Abstract:
Poly(ADP-ribose) polymerase (PARP)-1, a detector of single-strand breaks, plays a key role in the cellular response to DNA damage. PARP-1-deficient mice are hypersensitive to genotoxic agents and display genomic instability due to a DNA repair defect in the base excision repair pathway. A previous report suggested that PARP-1-deficient mice also had a severe telomeric dysfunction consisting of telomere shortening and increased end-to-end fusions (d'Adda di Fagagna, F., M.P. Hande, W.-M. Tong, P.M. Lansdorp, Z.-Q. Wang, and S.P. Jackson. 1999. NAT: Genet. 23:76-80). In contrast to that, and using a panoply of techniques, including quantitative telomeric (Q)-FISH, we did not find significant differences in telomere length between wild-type and PARP-1(-/)- littermate mice or PARP-1(-/)- primary cells. Similarly, there were no differences in the length of the G-strand overhang. Q-FISH and spectral karyotyping analyses of primary PARP-1(-/)- cells showed a frequency of 2 end-to-end fusions per 100 metaphases, much lower than that described previously (d'Adda di Fagagna et al., 1999). This low frequency of end-to-end fusions in PARP-1(-/)- primary cells is accordant with the absence of severe proliferative defects in PARP-1(-/)- mice. The results presented here indicate that PARP-1 does not play a major role in regulating telomere length or in telomeric end capping, and the chromosomal instability of PARP-1(-/)- primary cells can be explained by the repair defect associated to PARP-1 deficiency. Finally, no interaction between PARP-1 and the telomerase reverse transcriptase subunit, Tert, was found using the two-hybrid assay.read more
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Defective control of mitotic and post-mitotic checkpoints in poly(ADP-ribose) polymerase-1(-/-) fibroblasts after mitotic spindle disruption.
TL;DR: It is suggested that PARP may serve as a gaurdian angel of the genome even without exogenous DNA damage through its role in mitotic and post-mitotic G1 tetraploidy checkpoints.
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Poly(ADP-ribosylation) and Neoplastic Transformation: Effect of PARP Inhibitors
Francesca Donà,Ilaria Chiodi,Cristina Belgiovine,Tatiana Raineri,Roberta Ricotti,Chiara Mondello,Anna Ivana Scovassi +6 more
TL;DR: The data support an active involvement of poly(ADP-ribosylation) in neoplastic transformation and telomere length maintenance and confirm the relevant role of poly (ADP)ribosyation) inhibition for the treatment of cancer.
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Increased frequency of multiradial chromosome structures in mouse embryonic fibroblasts lacking functional Werner syndrome protein and poly(ADP-ribose) polymerase-1.
TL;DR: Results indicate that Wrn and PARP-1 enzymes may be part of a protein complex involved in the processing of DNA breaks that can ultimately lead to multiradial structures when both enzymes are nonfunctional.
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PARP1 is required for preserving telomeric integrity but is dispensable for A-NHEJ.
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TL;DR: While PARP1 does not participate significantly in DNA DSB repair itself, it does prevent the incidence of telomeric DSBs, which, in turn, can drive genomic instability.
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TL;DR: Results indicate that telomerase is essential for telomere length maintenance but is not required for establishment of cell lines, oncogenic transformation, or tumor formation in mice.
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