PARP1

  • OMIM: 173870
  • MGI: 1340806

Poly (ADP-ribose ) polymerase 1 (PARP -1) is an endogenous enzyme which is involved in DNA repair. Inhibition of the enzyme leads to breaks in single-stranded DNA ( ssDNA) only using homologous recombination can be solved. Therefore possibly cancer cells, which often homologous recombination is defective, be with substances that inhibit PARP -1, killed. The proteolytic degradation of PARP-1 by caspase -3 is an intermediate step of programmed cell death (apoptosis). In different species, the longevity of the cells with the PARP -1 activity is correlated. PARP-1 and is active in neurons that are part of the long-term memory. In the mouse model has also been found that overexpression of PARP -1 and consequent lack of energy, the mechanism for the toxicity of the Streptozotocins for pancreatic cells. PARP-1 - free mice show telomere shortening and lack of stability in the whole genome.

PARP -1 is a member of a group of 17 enzymes that have partially different structures and functions in the cell. Various PARPs are also indispensable in the spindle apparatus. PARP-1 contains 1,013 amino acids and has a molar mass of 113.2 kDa. Structurally it consists of three domains: a DNA binding zinc finger domain at the N -terminal end, a central automodification domain and a NAD -binding domain at the C -terminus. The for PARP-1 and other proteins encoding PARP gene is 43 kb long and contains 23 exons.

Catalyzed PARP-1 ADP- ribosylation of Chromatinproteinen ( such as histone H1 ) is occurring in all eukaryotic post-translational modification that is particularly useful for DNA breaks in response and have a role in DNA repair and recovery of the cell from damage alludes to the DNA. Every single Ribosylierungsschritt, of which about 60 to 80 take place at an acceptor, consumes one molecule of NAD . In the repaired cells therefore is lack of this substance.

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