1. Inhibition of Aurora-B kinase activity by poly(ADP-ribosyl)ation in response to DNA damage
- Author
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Josiane Ménissier-de Murcia, Lucia Monaco, Gilbert de Murcia, Romain Loury, Ullas Kolthur-Seetharam, Paolo Sassone-Corsi, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I
- Subjects
Poly Adenosine Diphosphate Ribose ,Histones/metabolism ,Poly (ADP-Ribose) Polymerase-1 ,Proteins/*metabolism ,Histones ,Mice ,0302 clinical medicine ,Aurora Kinases ,Chlorocebus aethiops ,Aurora Kinase B ,MESH: Animals ,MESH: Proteins ,Phosphorylation ,Non-U.S. Gov't ,DNA-PKcs ,Aurora Kinase A ,MESH: Histones ,0303 health sciences ,Multidisciplinary ,histone h3 ,mitosis ,phosphorylation ,poly(adp-ribose) polymerase-1 ,biology ,Poly Adenosine Diphosphate Ribose/*metabolism ,Blotting ,Biological Sciences ,MESH: COS Cells ,MESH: Poly Adenosine Diphosphate Ribose ,030220 oncology & carcinogenesis ,COS Cells ,Protein-Serine-Threonine Kinases/*metabolism ,Casein kinase 2 ,Poly(ADP-ribose) Polymerases ,Western ,DNA damage ,DNA repair ,Blotting, Western ,Protein Serine-Threonine Kinases ,Research Support ,MESH: Protein-Serine-Threonine Kinases ,Cercopithecus aethiops ,03 medical and health sciences ,Animals ,Immunoprecipitation ,MESH: Blotting, Western ,Comparative Study ,CHEK1 ,Kinase activity ,MESH: Mice ,030304 developmental biology ,MESH: DNA Damage ,MESH: Phosphorylation ,MESH: Immunoprecipitation ,Cyclin-dependent kinase 2 ,MESH: Poly(ADP-ribose) Polymerases ,Proteins ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Molecular biology ,MESH: Cercopithecus aethiops ,Poly(ADP-ribose) Polymerases/*metabolism ,biology.protein ,NIH 3T3 Cells ,Cyclin-dependent kinase 9 ,DNA Damage ,MESH: NIH 3T3 Cells - Abstract
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.
- Published
- 2005
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