Genomic instability in a PARP-1(-/-) cell line expressing PARP-1 DNA-binding domain.

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.

authors

Cayuela ML,Carrillo A,Ramirez P,Parrilla P,Yélamos J

doi

10.1006/bbrc.2001.5178

subject

Has Abstract

pub_date

2001-07-13 00:00:00

pages

289-94

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006291X01951782

journal_volume

285

pub_type

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