title: Nuclear localization of Beclin 1 promotes radiation-induced DNA damage repair independent of autophagy.
abstract: Beclin 1 is a well-established core mammalian autophagy protein that is embryonically indispensable and has been presumed to suppress oncogenesis via an autophagy-mediated mechanism. Here, we show that Beclin 1 is a prenatal primary cytoplasmic protein but rapidly relocated into the nucleus during postnatal development in mice. Surprisingly, deletion of beclin1 in in vitro human cells did not block an autophagy response, but attenuated the expression of several DNA double-strand break (DSB) repair proteins and formation of repair complexes, and reduced an ability to repair DNA in the cells exposed to ionizing radiation (IR). Overexpressing Beclin 1 improved the repair of IR-induced DSB, but did not restore an autophagy response in cells lacking autophagy gene Atg7, suggesting that Beclin 1 may regulate DSB repair independent of autophagy in the cells exposed to IR. Indeed, we found that Beclin 1 could directly interact with DNA topoisomerase IIβ and was recruited to the DSB sites by the interaction. These findings reveal a novel function of Beclin 1 in regulation of DNA damage repair independent of its role in autophagy particularly when the cells are under radiation insult.
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Yan
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Xu
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China.|Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, The First Affiliated Hospital, Soochow University School of Medicine, Suzhou 215123, China.|Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas Medical Sciences, Little Rock, Arkansas 72205, USA.
authors.forename: Suping
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China.
authors.forename: Jialing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China.
authors.forename: Gaoyue
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China.
authors.forename: Chaorong
authors.initials: C
authors.lastname: Ge
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China.
authors.forename: Ni
authors.initials: N
authors.lastname: An
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas Medical Sciences, Little Rock, Arkansas 72205, USA.
authors.forename: Daohong
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China.|Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, The First Affiliated Hospital, Soochow University School of Medicine, Suzhou 215123, China.
authors.forename: Na
authors.initials: N
authors.lastname: Yuan
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China.|Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, The First Affiliated Hospital, Soochow University School of Medicine, Suzhou 215123, China.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001343:Autophagy / Q000235:genetics*; D000071186:Beclin-1 / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D051379:Mice; D041681:NIH 3T3 Cells; D011839:Radiation, Ionizing
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D004268:DNA-Binding Proteins