The defect in the AT-like hamster cell mutants is complemented by mouse chromosome 9 but not by any of the human chromosomes

Wim Jongmans, Gerald W.C.T. Verhaegh, Nicolaas G.J. Jaspers, Peter Demant, Adayapalam T. Natarajan, Yosef Shiloh, Mitsuo Oshimura, Eric J. Stanbridge, Raghbir S. Athwal, Andrew P. Cuthbert, Robert F. Newbold, Paul H.M. Lohman, Małgorzata Z. Zdzienicka*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

X-ray-sensitive Chinese hamster V79 cells mutants, V-C4, V-E5 and V-G8, show an abnormal response to X-ray-induced DNA damage. Like ataxia telangiectasia (AT) cells, they display increased cell killing, chromosomal instability and a diminished inhibition of DNA synthesis following ionizing radiation. To localize the defective hamster gene (XRCC8) on the human genome, human chromosomes were introduced into the AT-like hamster mutants, by microcell mediated chromosome transfer. Although, none of the human chromosomes corrected the defect in these mutants, the defect was corrected by a single mouse chromosome, derived from the A9 microcell donor cell line. In four independent X-ray-resistant microcell hybrid clones of V-E5, the presence of the mouse chromosome was determined by fluorescent in situ hybridization, using a mouse cot-1 probe. By PCR analysis with primers specific for different mouse chromosomes and Southern blot analysis with the mouse Ldlr probe, the mouse chromosome 9, was identified in all four X-ray-resistant hybrid clones. Segregation of the mouse chromosome 9 from these hamster-mouse microcell hybrids led to the loss of the regained X-ray-resistance, confirming that mouse chromosome 9 is responsible for complementation of the defect in V-E5 cells. The assignment of the mouse homolog of the ATM gene to mouse chromosome 9, and the presence of this mouse chromosome only in the radioresistant hamster cell hybrids suggest that the hamster AT-like mutants are homologous to AT, although they are not complemented by human chromosome 11.

Original languageEnglish
Pages (from-to)91-102
Number of pages12
JournalMutation Research - DNA Repair
Volume364
Issue number2
DOIs
StatePublished - 18 Oct 1996

Keywords

  • Ataxia-telangiectasia
  • Microcell fusion
  • Mouse ATM homolog
  • Mouse chromosome 9
  • Radioresistant DNA synthesis
  • Radiosensitive hamster cell mutant

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