ATM-mediated response to DNA double strand breaks in human neurons derived from stem cells

Sharon Biton, Michal Gropp, Pavel Itsykson, Yaron Pereg, Leonid Mittelman, Karl Johe, Benjamin Reubinoff, Yosef Shiloh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Ataxia-telangiectasia (A-T) is a multi-system genomic instability syndrome that is caused by loss or inactivation of the ATM protein kinase. ATM is largely nuclear in proliferating cells, and activates an extensive network of pathways in response to double strand breaks (DSBs) in the DNA by phosphorylating key proteins in these pathways. The prominent symptom of A-T is neuronal degeneration, making the elucidation of ATM's functions in neurons essential to understanding the disease. It has been suggested that ATM is cytoplasmic in neurons and functions in processes that are not associated with the DNA damage response. Recently we showed that in human neuron-like cells obtained by in vitro differentiation of neuroblastomas, ATM was largely nuclear and mediated the DSB response as in proliferating cells. We have now extended these studies to two additional model systems: neurons derived from human embryonic stem cells, and cortical neurons derived from neural stem cells. The results substantiate the notion that ATM is nuclear in human neurons and mediates the DSB response, the same as it does in proliferating cells. We present here unique and powerful model systems to further study the ATM-mediated network in neurons.

Original languageEnglish
Pages (from-to)128-134
Number of pages7
JournalDNA Repair
Issue number1
StatePublished - 4 Jan 2007


FundersFunder number
A-T Ease Foundation
National Institutes of Health
National Institute of Neurological Disorders and StrokeR01NS031763
Dr. Ralph and Marian Falk Medical Research Trust
Medical Research Foundation


    • ATM
    • Ataxia-telangiectasia
    • DNA damage response
    • Embryonic stem cells
    • Neural stem cells
    • Neurons


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