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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TLDR
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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How Shelterin Protects Mammalian Telomeres
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TL;DR: Recent experiments have revealed how shelterin represses the ATM and ATR kinase signaling pathways and hides chromosome ends from nonhomologous end joining and homology-directed repair.
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Regulation of Telomerase by Telomeric Proteins
TL;DR: The details of telomerase and its regulation by the telomere are discussed, including single-stranded DNA-binding proteins (POT1 in humans and Cdc13 in budding yeast), which have been proposed to contribute to the recruitment of telomersase and may also regulate the extent or frequency of elongation.
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Noncoding RNA NORAD Regulates Genomic Stability by Sequestering PUMILIO Proteins.
Sungyul Lee,Florian Kopp,Tsung Cheng Chang,Anupama Sataluri,Beibei Chen,Sushama Sivakumar,Hongtao Yu,Yang Xie,Joshua T. Mendell +8 more
TL;DR: The initial functional analysis of a poorly characterized human lncRNA that is induced after DNA damage is described, introducing a mechanism that regulates the activity of a deeply conserved and highly dosage-sensitive family of RNA binding proteins and reveal unanticipated roles for a lnc RNA and PUMILIO proteins in the maintenance of genomic stability.
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Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin
Susana Gonzalo,Marta García-Cao,Mario F. Fraga,Gunnar Schotta,Antoine H.F.M. Peters,Shane E. Cotter,Raúl Eguı́a,Douglas C. Dean,Douglas C. Dean,Manel Esteller,Thomas Jenuwein,Maria A. Blasco +11 more
TL;DR: Observations indicate that the RB1 family is involved in maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin, linking tumour suppression and the epigenetic definition of chromatin.
References
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Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells
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Tankyrase, a Poly(ADP-Ribose) Polymerase at Human Telomeres
TL;DR: Tankyrase, a protein with homology to ankyrins and to the catalytic domain of poly(adenosine diphosphate-ribose) polymerase (PARP), was identified and localized to human telomeres.
Journal ArticleDOI
XRCC1 Is Specifically Associated with Poly(ADP-Ribose) Polymerase and Negatively Regulates Its Activity following DNA Damage
Murielle Masson,Claude Niedergang,Valérie Schreiber,Sylviane Muller,Josiane Ménissier-de Murcia,Gilbert de Murcia +5 more
TL;DR: The results provide strong evidence that PARP is a member of a BER multiprotein complex involved in the detection of DNA interruptions and possibly in the recruitment of XRCC1 and its partners for efficient processing of these breaks in a coordinated manner.
Journal ArticleDOI
Mice lacking ADPRT and poly(ADP-ribosyl)ation develop normally but are susceptible to skin disease.
Zhao-Qi Wang,Bernhard Auer,Laura Stingl,H. Berghammer,D. Haidacher,Manfred Schweiger,Erwin F. Wagner +6 more
TL;DR: The generation of viableADPRT-/-mice negates an essential role for this enzyme in normal chromatin function, but the impaired proliferation and the onset of skin lesions in older mice suggest a function for ADPRT in response to environmental stress.