4AV1

Crystal structure of the human PARP-1 DNA binding domain in complex with DNA

Summary for 4AV1

• Entry DOI: 10.2210/pdb4av1/pdb
• Related: 1UK0 1UK1 1WOK 2COK 2CR9 2CS2
• Descriptor: POLY [ADP-RIBOSE] POLYMERASE 1, 5'-D(*AP*AP*GP*TP*GP*TP*TP*GP*CP*AP*TP*TP)-3', 5'-D(*TP*AP*AP*TP*GP*CP*AP*AP*CP*AP*CP*TP)-3', ... (5 entities in total)
• Functional Keywords: transferase, parp1, dna-binding domain, dbd, dna repair, cancer, poly- adp(ribosyl)ation
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus: P09874
• Total number of polymer chains: 6
• Total formula weight: 107959.48

Authors

Ali, A.A.E.,Timinszky, G.,Arribas-Bosacoma, R.,Kozlowski, M.,Hassa, P.O.,Hassler, M.,Ladurner, A.G.,Pearl, L.H.,Oliver, A.W. (deposition date: 2012-05-23, release date: 2012-06-13, Last modification date: 2024-05-01)

Primary citation

Ali, A.A.E.,Timinszky, G.,Arribas-Bosacoma, R.,Kozlowski, M.,Hassa, P.O.,Hassler, M.,Ladurner, A.G.,Pearl, L.H.,Oliver, A.W.
The Zinc-Finger Domains of Parp1 Cooperate to Recognise DNA Strand-Breaks
Nat.Struct.Mol.Biol., 19:685-, 2012

PubMed Abstract: Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. Upon activation at sites of DNA damage, PARP1 modifies itself and other proteins by covalent addition of long, branched polymers of ADP-ribose, which in turn recruit downstream DNA repair and chromatin remodeling factors. PARP1 recognizes DNA damage through its N-terminal DNA-binding domain (DBD), which consists of a tandem repeat of an unusual zinc-finger (ZnF) domain. We have determined the crystal structure of the human PARP1-DBD bound to a DNA break. Along with functional analysis of PARP1 recruitment to sites of DNA damage in vivo, the structure reveals a dimeric assembly whereby ZnF1 and ZnF2 domains from separate PARP1 molecules form a strand-break recognition module that helps activate PARP1 by facilitating its dimerization and consequent trans-automodification.

PubMed: 22683995
DOI: 10.1038/NSMB.2335

Experimental method

X-RAY DIFFRACTION (3.1 Å)