Stemness factor Sall4 is required for DNA damage response in embryonic stem cells

The Journal of Cell Biology
Jianhua XiongYang Xu

Abstract

Mouse embryonic stem cells (ESCs) are genetically more stable than somatic cells, thereby preventing the passage of genomic abnormalities to their derivatives including germ cells. The underlying mechanisms, however, remain largely unclear. In this paper, we show that the stemness factor Sall4 is required for activating the critical Ataxia Telangiectasia Mutated (ATM)-dependent cellular responses to DNA double-stranded breaks (DSBs) in mouse ESCs and confer their resistance to DSB-induced cytotoxicity. Sall4 is rapidly mobilized to the sites of DSBs after DNA damage. Furthermore, Sall4 interacts with Rad50 and stabilizes the Mre11-Rad50-Nbs1 complex for the efficient recruitment and activation of ATM. Sall4 also interacts with Baf60a, a member of the SWI/SNF (switch/sucrose nonfermentable) ATP-dependent chromatin-remodeling complex, which is responsible for recruiting Sall4 to the site of DNA DSB damage. Our findings provide novel mechanisms to coordinate stemness of ESCs with DNA damage response, ensuring genomic stability during the expansion of ESCs.

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Citations

Jan 19, 2016·Journal of Molecular Histology·Liliang HaoQi Su
Jul 12, 2016·The FEBS Journal·Hyun Ju LeeDavid Vilchez
Sep 12, 2016·Cellular and Molecular Life Sciences : CMLS·Xuemei FuYang Xu
Jan 1, 2016·Npj Regenerative Medicine·Jami R EricksonKaren Echeverri
Jun 4, 2020·Cancer Cell International·Meng ShaoXu Zhang
Jan 23, 2020·Proceedings of the National Academy of Sciences of the United States of America·Peng LiLingyi Chen
Mar 6, 2017·Molecular Medicine Reports·Wiktoria Maria SuchorskaMagdalena Łukjanow
Jun 10, 2021·Head and Neck Pathology·Margaret L ComptonKim A Ely

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Methods Mentioned

BETA
coimmunoprecipitation
immunoprecipitation
pull-down
acetylation
Assay
transfection
PCR
transfections
ChIP

Software Mentioned

SpectrumMill
Spectrum Mill
Excel
ImageJ
FluoView
Comet Assay IV

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