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  • Title: Genomic instability in a PARP-1(-/-) cell line expressing PARP-1 DNA-binding domain.
    Author: Cayuela ML, Carrillo A, Ramirez P, Parrilla P, Yélamos J.
    Journal: Biochem Biophys Res Commun; 2001 Jul 13; 285(2):289-94. PubMed ID: 11444840.
    Abstract:
    Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear DNA binding protein that participates in processes involving nicking and resealing DNA strands. A genomically unstable subpopulation of PARP-1(-/-) cells has recently been described, which disappears after stable transfection of the cells with complete PARP-1 cDNA. Here we investigate the role played by PARP-1 in the maintenance of genomic stability, independently of its enzymatic activity. We used a PARP-1-deficient cell line to express a DNA construct encoding the PARP-1 DNA-binding domain (DBD) fragment and one encoding the mutant DBDbd-, defective in binding to DNA strand breaks. We found that, in the absence of DNA damage, expression of DBD or DBDbd- mutant induces increased genomic instability in the PARP-1(-/-) cells. These results suggest that the DBD fragment of PARP-1, apart from its classical role of nick detection and DNA binding, is likely to participate in molecular complexes with proteins involved in genomic integrity.
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