Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of poly (ADP-ribose) polymerase -1 (PARP-1) is an early DNA damage response event that, together with phosphorylation of p53, prompts various cellular functions important in the maintenance of the genome stability. In mammalian cells, DSB are repaired by nonhomologous end-joining (NHEJ) and by homologous recombination (HR). To investigate the role of PARP-1 in HR, CHO-K1 wild type and xrs-6 mutant cell line were transfected with pLrec plasmids which carry two nonfunctional copies of the beta-galactosidase (lacZ) gene in a tandem array. In result of HR they can give rise to a functional copy of beta-galactosidase. To test whether PARP-1 affects the frequency of spontaneous and induced recombination repair, we treated CHO-K1 and xrs6 clones carrying chromosomally integrated pLrec with the PARP-1 inhibitor 3-aminobenzamide (3AB). Our results show that the spontaneous homologous intrachromosomal recombination frequency between the two lacZ copies was almost two orders of magnitude higher in xrs6 cells than in CHO-K1 cells, but that it was not affected by 3AB treatment. Induction of DNA damage by irradiation or electroporation of restriction enzymes did not significantly increase the recombination frequency. Furthermore, in both the cell lines, the effect of PARP-1 inhibition on DSB repair was examined using the neutral comet assay. There was no effect of 3AB treatment on DSB rejoining after 10 Gy irradiation. The results presented support the conclusion that PARP-1 is not directly involved in HR.
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PMID:Inhibition of poly(ADP-ribose)polymerase does not affect the recombination events in CHO xrs6 and wild type cells. 1696 95

It has been reported that p53 acetylation, which promotes cellular senescence, can be regulated by the NAD(+)-dependent deacetylase SIRT1, the human homolog of yeast Sir2, a protein that modulates lifespan. To clarify the role of SIRT1 in cellular senescence induced by oxidative stress, we treated normal human diploid fibroblast TIG-3 cells with H(2)O(2) and examined DNA cleavage, depletion of intracellular NAD(+), expression of p21, SIRT1, and acetylated p53, cell cycle arrest, and senescence-associated beta-galactosidase (SA-beta-gal) activity. DNA cleavage was observed immediately in TIG-3 cells treated with H(2)O(2), though no cell death was observed. NAD(+) levels in TIG-3 cells treated with H(2)O(2) were also decreased significantly. Pre-incubation with the poly (ADP-ribose) polymerase (PARP) inhibitor resulted in preservation of intracellular NAD(+) levels. The amount of acetylated p53 was increased in TIG-3 cells at 4h after H(2)O(2) treatment, while there was little to no decrease in SIRT1 protein expression. The expression level of p21 was increased at 12h and continued to increase for up to 24h. Additionally, exposure of TIG-3 cells to H(2)O(2) induced cell cycle arrest at 24h and increased SA-beta-gal activity at 48h. This pathway likely plays an important role in the acceleration of cellular senescence by oxidative stress.
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PMID:H2O2 accelerates cellular senescence by accumulation of acetylated p53 via decrease in the function of SIRT1 by NAD+ depletion. 1759 14

In response to ultraviolet radiation (UV), mammalian cells rapidly activate a nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP), and we recently showed that one of the causes for PARP-activation is UV-induced direct DNA photolesions which are repaired by nucleotide excision repair process (NER). To determine whether PARP can play a role in NER, we stably depleted PARP in NER-proficient human skin fibroblasts GM637 by DNA vector-based RNAi. In these cells, we examined host cell reactivation (HCR) of UVB or UVC-irradiated recombinant adenovirus AdCA35lacZ, encoding a beta-galactosidase (beta-gal) reporter gene. The depletion of PARP decreased the HCR of UVB- or UVC-damaged reporter gene to a similar extent, indicating the role of PARP in NER. Moreover, PARP-depletion reduced the HCR capacity of the NER-competent GM637 cells to a level closer to that in the XP-C and CS-B cell lines, which are deficient in the lesion recognition steps of the global genome repair (GGR) and transcription-coupled repair (TCR) sub-pathways of NER, respectively. In order to identify the potential role of PARP in these two sub-pathways of NER from that of its known role in base excision repair (BER) of UVB-induced oxidant damage, we depleted PARP from XP-C and CS-B cells and examined HCR of the reporter gene damaged by UVB, UVC or photoactivated methylene blue, the latter causing predominantly 8-oxo-2'-deoxyguanosine damage that is repaired by BER. Interestingly, a decreased HCR due to PARP-depletion was observed in both the NER-deficient cell lines in response to virus damaged by these three agents, albeit with different kinetics from 12 to 44h after infection. The role of PARP in NER was highlighted by a decreased clonogenic survival of UV-irradiated NER-competent GM637 cells depleted of PARP. Our results, while confirming the role of PARP in base excision repair, suggest a novel role of PARP in both the GGR and TCR sub-pathways of NER.
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PMID:Depletion of poly(ADP-ribose) polymerase-1 reduces host cell reactivation of a UV-damaged adenovirus-encoded reporter gene in human dermal fibroblasts. 1828 44


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