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The genesis of cerebellar interneurons and the prevention of neural DNA damage require XRCC1

journal contribution
posted on 2023-06-07, 21:33 authored by Youngsoo Lee, Sachin Katyal, Yang Li, Sherif F El-Khamisy, Helen R Russell, Keith CaldecottKeith Caldecott, Peter J McKinnon
Defective responses to DNA single strand breaks underlie various neurodegenerative diseases. However, the exact role of this repair pathway during the development and maintenance of the nervous system is unclear. Using murine neural-specific inactivation of Xrcc1, a factor that is critical for the repair of DNA single strand breaks, we found a profound neuropathology that is characterized by the loss of cerebellar interneurons. This cell loss was linked to p53-dependent cell cycle arrest and occurred as interneuron progenitors commenced differentiation. Loss of Xrcc1 also led to the persistence of DNA strand breaks throughout the nervous system and abnormal hippocampal function. Collectively, these data detail the in vivo link between DNA single strand break repair and neurogenesis and highlight the diverse consequences of specific types of genotoxic stress in the nervous system.

History

Publication status

  • Published

Journal

Nature Neuroscience

ISSN

1097-6256

Publisher

Nature Publishing Group

Issue

8

Volume

12

Page range

973-U35

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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    University of Sussex (Publications)

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