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


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.

SUBMITTER: Xiong J 

PROVIDER: S-EPMC4347641 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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

Xiong Jianhua J   Todorova Dilyana D   Su Ning-Yuan NY   Kim Jinchul J   Lee Pei-Jen PJ   Shen Zhouxin Z   Briggs Steven P SP   Xu Yang Y  

The Journal of cell biology 20150301 5


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 cytoto  ...[more]

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