کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10824029 | 1061963 | 2005 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Ionizing radiations in Caenorhabditis elegans induce poly(ADP-ribosyl)ation, a conserved DNA-damage response essential for survival
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کلمات کلیدی
1,5-dihydroxyisoquinoline3ABPARPDNA-PKPMSFDHQPARGIPTGDBDisopropylthiogalactosidePJ34VPARP3-Aminobenzamide - 3-آمینوبنزامیدDMSO - DMSOEDTA - اتیلن دی آمین تترا استیک اسید ethylene diamine tetraacetic acid - اتیلن دیامین تتراستیک اسیدpost-translational modification - اصلاح post-translationalionizing radiation - تابش یوننده یا پرتوهای یونیزانATM - خودپردازDNA binding domain - دامنه اتصال DNAten - دهDimethyl sulfoxide - دیمتیل سولفواکسیدPME - شرکتهای کوچک و متوسطPhenylmethylsulphonylfluoride - فنیل متیل سولفونیل فلورایدPARP inhibitors - مهار کننده های PARPNAD - نادانSurvival rate - نرخ بقاnicotinamide adenine dinucleotide - نیکوتین آمید adenine dinucleotideDNA-dependent protein kinase - وابسته به پروتئین کیناز وابسته به DNApADPr - پدریPoly(ADP-ribose) polymerase - پلیمر (ADP-ribose) پلیمرازNematode - کرمهای لولهایpoly(ADP-ribose) glycohydrolase - گلیکا هیدرولاز پلی (ADP-ribose)
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Poly(ADP-ribosyl)ation is one of the first responses to DNA damage in mammals. Although it is involved in base excision repair, its exact role has not been ascertained yet. Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 mediate most of the poly(ADP-ribosyl)ation response in mammals and are well conserved in evolution. Their respective homologues PME-1 and PME-2 are found in the nematode Caenorhabditis elegans, a well-known genetically tractable model currently used in DNA damage response research. Here we report the functional analysis of PME-1 and PME-2 in presence of DNA damage. Worms irradiated with high doses of ionizing radiations displayed a sharp drop in their NAD+ content immediately after treatment, and a biphasic increase in poly(ADP-ribose). The physiological importance of the poly(ADP-ribosyl)ation response was highlighted when worms were preincubated with mammalian PARP inhibitors (3AB, DHQ, PJ34) and irradiated. The embryonic survival rate of the progeny was significantly decreased in a dose-dependent manner. The inhibitor 3AB had a weak effect on embryonic survival, followed closely by DHQ. However, PJ34, a member of the phenantridinone family, was very effective even when used at low concentration (100Â nM). In vitro PARP assay using recombinant PME-1 and PME-2 showed a similar pattern of inhibition where 3AB and DHQ were weak inhibitors, and PJ34 a stronger one. Inhibitors affect mostly the poly(ADP-ribose) polymers elongation at high concentrations. These results suggest that poly(ADP-ribosyl)ation in response to DNA damage is an ancient and very important biochemical process protecting DNA from deleterious modification.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 4, Issue 7, 12 July 2005, Pages 814-825
Journal: DNA Repair - Volume 4, Issue 7, 12 July 2005, Pages 814-825
نویسندگان
Florence Dequen, Steve N. Gagnon, Serge Desnoyers,