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. © 2005 by The National Academy of Sciences of the USA.
Inhibition of Aurora-B kinase activity by poly(ADP-ribosyl)ation in response to DNA damage / Monaco, Lucia; U., Kolthur Seetharan; R., Loury; Mnissier De J., Murcia; G., De Murcia; P., Sassone Corsi. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 102:40(2005), pp. 14244-14248. [10.1073/pnas.0506252102]
Inhibition of Aurora-B kinase activity by poly(ADP-ribosyl)ation in response to DNA damage
MONACO, Lucia;
2005
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. © 2005 by The National Academy of Sciences of the USA.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
