DNA-PKcs, ATM, and ATR Interplay Maintains Genome Integrity During Neurogenesis

Overview

Journal J Neurosci

Specialty Neurology

Date 2017 Jan 27

PMID 28123024

Citations 41

Authors

Vanessa Enriquez-Rios

Lavinia C Dumitrache

Susanna M Downing

Yang Li

Eric J Brown

Helen R Russell

Peter J McKinnon

Affiliations

Soon will be listed here.

Abstract

Significance Statement: The DNA damage response (DDR) is essential for prevention of a broad spectrum of different human neurologic diseases. However, a detailed understanding of the DDR at a physiological level is lacking. In contrast to many in vitro cellular studies, here we demonstrate independent biological roles for the DDR kinases DNA-PKcs, ATM, and ATR during neurogenesis. We show that DNA-PKcs is central to DNA repair in nonproliferating cells, and restricts DNA damage accumulation, whereas ATR controls damage-induced G checkpoint control and apoptosis in proliferating cells. Conversely, ATM is critical for controlling apoptosis in immature noncycling neural cells after DNA damage. These data demonstrate functionally distinct, but cooperative, roles for each kinase in preserving genome stability in the nervous system.

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