Male sterility and enhanced radiation sensitivity in TLS(-/-) mice

Masahiko Kuroda, John Sok, Lisa Webb, Heidi Baechtold, Fumihiko Urano, Yin Yin, Peter Chung, Dirk G. De Rooij, Alexandre Akhmedov, Terry Ashley, David Ron

Research output: Contribution to journalArticlepeer-review

175 Scopus citations

Abstract

TLS (also known as FUS) is an RNA-binding protein that contributes the N-terminal half of fusion oncoproteins implicated in the development of human liposarcomas and leukemias. Here we report that male mice homozygous for an induced mutation in TLS are sterile with a marked increase in the number of unpaired and mispaired chromosomal axes in premeiotic spermatocytes. Nuclear extracts from TLS(-/-) testes lack an activity capable of promoting pairing between homologous DNA sequences in vitro, and TLS(-/-) mice and embryonic fibroblasts exhibit increased sensitivity to ionizing irradiation. These results are consistent with a role for TLS in homologous DNA pairing and recombination.

Original languageEnglish
Pages (from-to)453-462
Number of pages10
JournalEMBO Journal
Volume19
Issue number3
DOIs
StatePublished - Feb 1 2000

Keywords

  • Fusion oncoproteins
  • Homologous recombination
  • Spermatogenesis
  • TLS deficiency

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