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The human poly (ADP-ribose) polymerase (PARP-1, 113kDa). • Gene Location chromosome 1q41- q42 Size 43 kb Structure 23 exons Promoter lacks typical regulatory elements like (TATA, CAAT boxes) Sp 1 & AP- 2 binding site s; GC boxes
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The human poly (ADP-ribose) polymerase (PARP-1, 113kDa) • Gene Location chromosome 1q41- q42 Size 43 kb Structure 23 exons Promoter lacks typical regulatory elements like (TATA, CAAT boxes) Sp 1 & AP- 2 binding site s; GC boxes • mRNA 3.6kb. No transcriptional induction following DNA damage • Protein 1014 amino acids ; Mr = 113,153. Nuclear & nucleolar localization Abundant in the immune system, germinal cells, brain • Motifs Zinc fingers : 2 [C-x2-C-x28,30-H-x2-C] (nick binding) Bipartite NLS : KRK-x11-KKKSKK (nuclear localization) BRCT motif ; NAD+ binding fold • DNA binding ss DNA breaks (strong activator) >> ds breaks • Substrate NAD+ (Km= 40 M) • Inhibitors Nicotinamide analogues: 3-Aminobenzamide ; PD128763 ; NU1025 • Target Proteins • (Automodification) PARP-1 (BRCT motif) • (Heteromodification) Histones H1, H2B Topoisomerases I, II , Lamin B RPA (70 and 34 kDa), SV40 T-Ag (B23) Numatrin, (C23) Nucleolin