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.
References
Mar 4, 2003·Nature Reviews. Cancer·Yosef Shiloh
Jun 27, 2003·Cytogenetic and Genome Research·J KohlhaseA Kispert
Dec 29, 2005·Nature Genetics·Kazuko Koshiba-TakeuchiBenoit G Bruneau
Mar 21, 2006·Developmental Biology·Dylan Sweetman, Andrea Münsterberg
May 26, 2006·Nature Reviews. Molecular Cell Biology·Eran Meshorer, Tom Misteli
Jun 23, 2006·Development·Masayo Sakaki-YumotoRyuichi Nishinakamura
Aug 15, 2006·Nature·Manuela PellegriniAndré Nussenzweig
Aug 18, 2006·Mutation Research·Y HongP J Stambrook
Apr 10, 2007·Nature Cell Biology·Hoseok SongYang Xu
Dec 11, 2007·Oncogene·J-H Lee, T T Paull
Apr 1, 2008·Experimental Cell Research·Elisia D Tichy, Peter J Stambrook
Sep 13, 2008·Cell Stem Cell·Dirk HockemeyerRudolf Jaenisch
Dec 17, 2008·Nature Cell Biology·Yong-Chul KimMichael Bustin
Dec 23, 2008·Journal of Medicinal Chemistry·Franco ChimentiPatrizia Filetici
Mar 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lena HoGerald R Crabtree
Mar 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lena HoGerald R Crabtree
Apr 8, 2009·Stem Cells·Shunsuke YuriRyuichi Nishinakamura
Mar 13, 2010·The EMBO Journal·Han-Sae LeeJongbum Kwon
Jan 22, 2011·Nature Reviews. Molecular Cell Biology·Travis H Stracker, John H J Petrini
Feb 1, 2012·Epigenetics & Chromatin·Hannes LansWim Vermeulen
May 5, 2012·Current Opinion in Hematology·Jianchang YangYupo Ma
Sep 18, 2012·Cell·Yosef BuganimRudolf Jaenisch
Sep 22, 2012·Biochimica Et Biophysica Acta·Pratik NagariaFeyruz V Rassool
Oct 2, 2013·Proceedings of the National Academy of Sciences of the United States of America·Michael GoldsteinMichael B Kastan
Citations
Jan 19, 2016·Journal of Molecular Histology·Liliang HaoQi Su
Oct 24, 2015·Stem Cells and Development·Irma Virant-Klun
Feb 20, 2016·Gene·Hiro TatetsuLi Chai
Jul 12, 2016·The FEBS Journal·Hyun Ju LeeDavid Vilchez
Sep 12, 2016·Cellular and Molecular Life Sciences : CMLS·Xuemei FuYang Xu
Nov 8, 2016·Oncogenesis·X YuanW Xu
Aug 2, 2017·Oncogene·J KimY Xu
Oct 6, 2018·Cancer Science·Chiemi NakayamaKazuhiko Koike
Mar 25, 2019·Cancer Medicine·Xin NieGuoqing Hu
May 31, 2019·Stem Cells·Xin LiuYang Xu
Jan 9, 2018·Biomarker Research·Jianchang Yang
Jan 1, 2016·Npj Regenerative Medicine·Jami R EricksonKaren Echeverri
Mar 15, 2020·Protein & Cell·Shuxiang XuXuemei Fu
Sep 10, 2017·Journal of Neuro-oncology·Chuanjin LiuZiwei Du
Aug 8, 2019·Aging Cell·Liang-Jian ChenDong Zhang
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
Sep 21, 2019·Nature Communications·Jiajing ChenYunyu Shi
Jun 10, 2021·Head and Neck Pathology·Margaret L ComptonKim A Ely
Sep 24, 2021·Nature Communications·Lin WangPing Zheng