Parp1 hyperactivity couples DNA breaks to aberrant neuronal calcium signalling and lethal seizures

• Published in: EMBO reports Vol. 22; no. 5; pp. e51851 - n/a
• Main Authors: Komulainen, Emilia, Badman, Jack, Rey, Stephanie, Rulten, Stuart, Ju, Limei, Fennell, Kate, Kalasova, Ilona, Ilievova, Kristyna, McKinnon, Peter J, Hanzlikova, Hana, Staras, Kevin, Caldecott, Keith W
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.05.2021; Blackwell Publishing Ltd; John Wiley and Sons Inc
• Subjects: Aberration; Animals; Calcium; Calcium signalling; Defects; Deletion; Deoxyribonucleic acid; Deregulation; DNA; DNA damage; DNA repair; DNA Repair - genetics; DNA strand break; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Electrophysiological recording; EMBO13; EMBO24; EMBO27; Hippocampus; Hyperactivity; Life span; Mice; neurodegeneration; Neuroimaging; Neurological complications; Neurological diseases; Neurons; Neurons - metabolism; Poly (ADP-Ribose) Polymerase-1 - genetics; Poly (ADP-Ribose) Polymerase-1 - metabolism; Poly(ADP-ribose) polymerase; Proteins; Seizures; Seizures - genetics; Signaling; XRCC1; XRCC1 protein; neurodegeneration; seizures; XRCC1; poly(ADP-ribose) polymerase; DNA strand break

Defects in DNA single-strand break repair (SSBR) are linked with neurological dysfunction but the underlying mechanisms remain poorly understood. Here, we show that hyperactivity of the DNA strand break sensor protein Parp1 in mice in which the central SSBR protein Xrcc1 is conditionally deleted ( X...