Temporal activation of XRCC1-mediated DNA repair is essential for muscle differentiation

Transient DNA strand break formation has been identified as an effective means to enhance gene expression in living cells. In the muscle lineage, cell differentiation is contingent upon the induction of caspase-mediated DNA strand breaks, which act to establish the terminal gene expression program....

Full description

Saved in:
Bibliographic Details
Published in:Cell discovery 2016-01, Vol.2 (1), p.15041-15041, Article 15041
Main Authors: Al-Khalaf, Mohammad H, Blake, Leanne E, Larsen, Brian D, Bell, Ryan A, Brunette, Steve, Parks, Robin J, Rudnicki, Michael A, McKinnon, Peter J, Jeffrey Dilworth, F, Megeney, Lynn A
Format: Article
Language:English
Subjects:
631/136
631/337/1427/1429
Biomedical and Life Sciences
Cell Biology
Cell Culture
Cell Cycle Analysis
Cell Physiology
Life Sciences
Stem Cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Transient DNA strand break formation has been identified as an effective means to enhance gene expression in living cells. In the muscle lineage, cell differentiation is contingent upon the induction of caspase-mediated DNA strand breaks, which act to establish the terminal gene expression program. This coordinated DNA nicking is rapidly resolved, suggesting that myoblasts may deploy DNA repair machinery to stabilize the genome and entrench the differentiated phenotype. Here, we identify the base excision repair pathway component XRCC1 as an indispensable mediator of muscle differentiation. Caspase-triggered XRCC1 repair foci form rapidly within differentiating myonuclei, and then dissipate as the maturation program proceeds. Skeletal myoblast deletion of Xrcc1 does not have an impact on cell growth, yet leads to perinatal lethality, with sustained DNA damage and impaired myofiber development. Together, these results demonstrate that XRCC1 manages a temporally responsive DNA repair process to advance the muscle differentiation program.
ISSN:2056-5968
2056-5968
DOI:10.1038/celldisc.2015.41