4av1
From Proteopedia
Crystal structure of the human PARP-1 DNA binding domain in complex with DNA
Structural highlights
Function[PARP1_HUMAN] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.[1] [2] [3] [4] Publication Abstract from PubMedPoly(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. The zinc-finger domains of PARP1 cooperate to recognize DNA strand breaks.,Ali AA, Timinszky G, Arribas-Bosacoma R, Kozlowski M, Hassa PO, Hassler M, Ladurner AG, Pearl LH, Oliver AW Nat Struct Mol Biol. 2012 Jun 10;19(7):685-92. doi: 10.1038/nsmb.2335. PMID:22683995[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Human | Large Structures | Ali, A A.E | Arribas-Bosacoma, R | Hassa, P O | Hassler, M | Kozlowski, M | Ladurner, A G | Oliver, A W | Pearl, L H | Timinszky, G | Cancer | Dbd | Dna repair | Dna-binding domain | Parp1 | Transferase
