Ewing sarcoma gene EWS is essential for meiosis and B lymphocyte development.
Ewing sarcoma gene EWS encodes a putative RNA-binding protein with proposed roles in transcription and splicing, but its physiological role in vivo remains undefined. Here, we have generated Ews-deficient mice and demonstrated that EWS is required for the completion of B cell development and meiosis. Analysis of Ews(-/-) lymphocytes revealed a cell-autonomous defect in precursor B lymphocyte (pre-B lymphocyte) development. During meiosis, Ews-null spermatocytes were deficient in XY bivalent formation and showed reduced meiotic recombination, resulting in massive apoptosis and complete arrest in gamete maturation. Inactivation of Ews in mouse embryonic fibroblasts resulted in premature cellular senescence, and the mutant animals showed hypersensitivity to ionizing radiation. Finally, we showed that EWS interacts with lamin A/C and that loss of EWS results in a reduced lamin A/C expression. Our findings reveal essential functions for EWS in pre-B cell development and meiosis, with proposed roles in DNA pairing and recombination/repair mechanisms. Furthermore, we demonstrate a novel role of EWS in cellular senescence, possibly through its interaction and modulation of lamin A/C.
Li
Hongjie
H
Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Watford
Wendy
W
Li
Cuiling
C
Parmelee
Alissa
A
Bryant
Mark A
MA
Deng
Chuxia
C
O'Shea
John
J
Lee
Sean Bong
SB
D000818:Animals; D000831:Animals, Newborn; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D053595:Embryonic Stem Cells / Q000502:physiology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008540:Meiosis / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D034802:RNA-Binding Protein EWS / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D012189:Retrospective Studies; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D034802:RNA-Binding Protein EWS