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

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

Content Provider	Scilit
Author	Xiong, Jianhua Todorova, Dilyana Su, Ning-Yuan Kim, Jinchul Lee, Pei-Jen Shen, Zhouxin Briggs, Steven P. Xu, Yang
Copyright Year	2015
Description	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.
Related Links	http://europepmc.org/articles/pmc4347641?pdf=render https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347641/pdf http://jcb.rupress.org/content/208/5/513.full.pdf
Ending Page	520
Page Count	8
Starting Page	513
DOI	10.1083/jcb.201408106
Journal	Journal of Cell Biology
Issue Number	5
Volume Number	208
Language	English
Publisher	Rockefeller University Press
Publisher Date	2015-03-02
Access Restriction	Open
Subject Keyword	Cell Biology Somatic Chromatin Damage Embryonic Stem Cells Mouse Escs Stemness Sall4 Dsbs Rad50 Journal: Journal of Cell Biology (Vol- 208, Issue- 5)
Content Type	Text

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