Inhibition of Aurora-B kinase activity by poly(ADP-ribosyl)ation in response to DNA damage.
The cell cycle-regulated Aurora-B kinase is a chromosomal passenger protein that is implicated in fundamental mitotic events, including chromosome alignment and segregation and spindle checkpoint function. Aurora-B phosphorylates serine 10 of histone H3, a function that has been associated with mitotic chromatin condensation. We find that activation of poly(ADP-ribose) polymerase ... (PARP) 1 by DNA damage results in a rapid block of H3 phosphorylation. PARP-1 is a NAD(+)-dependent enzyme that plays a multifunctional role in DNA damage detection and repair and maintenance of genomic stability. Here, we show that Aurora-B physically and specifically associates with the BRCT (BRCA-1 C-terminal) domain of PARP-1. Aurora-B becomes highly poly(ADP-ribosyl)ated in response to DNA damage, a modification that leads to a striking inhibition of its kinase activity. The highly similar Aurora-A kinase is not regulated by PARP-1. We propose that the specific inhibition of Aurora-B kinase activity by PARP-1 contributes to the physiological response to DNA damage.
Mesh Terms:
Animals, Blotting, Western, COS Cells, Cercopithecus aethiops, DNA Damage, Histones, Immunoprecipitation, Mice, NIH 3T3 Cells, Phosphorylation, Poly Adenosine Diphosphate Ribose, Poly(ADP-ribose) Polymerases, Protein-Serine-Threonine Kinases, Proteins
Animals, Blotting, Western, COS Cells, Cercopithecus aethiops, DNA Damage, Histones, Immunoprecipitation, Mice, NIH 3T3 Cells, Phosphorylation, Poly Adenosine Diphosphate Ribose, Poly(ADP-ribose) Polymerases, Protein-Serine-Threonine Kinases, Proteins
Proc. Natl. Acad. Sci. U.S.A.
Date: Oct. 04, 2005
PubMed ID: 16179389
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