Correction of chromosomal instability and sensitivity to diverse mutagens by a cloned cDNA of the XRCC3 DNA repair gene

Robert S. Tebbs, Ying Zhao, James D. Tucker, Julia B. Scheerer, Michael J. Siciliano, Mona Hwang, Nan Liu, Randy J. Legerski, Larry H. Thompson

Research output: Contribution to journalArticlepeer-review

235 Scopus citations

Abstract

The mutagen-sensitive CHO line irs1SF was previously isolated on the basis of hypersensitivity to ionizing radiation and was found to be chromosomally unstable as well as cross-sensitive to diverse kinds of DNA-damaging agents. The analysis of somatic cell hybrids formed between irs1SF and human lymphocytes implicated a human gene (defined as XRCC3; x-ray repair cross- complementing), which partially restored mitomycin C resistance to the mutant. A functional cDNA that confers mitomycin C resistance was transferred to irs1SF cells by transforming them with an expression cDNA library and obtaining primary and secondary transformants. Functional cDNA clones were recovered from a cosmid library prepared from a secondary transformant. Transformants also showed partial correction of sensitivity to cisplatin and γ-rays, efficient correction of chromosomal instability, and substantially improved plating efficiency and growth rate. The XRCC3 cDNA insert is ≃2.5 kb and detects an ≃3.0-kb mRNA on Northern blots. The cDNA was mapped by fluorescence in situ hybridization to human chromosome 14q32.3, which was consistent with the chromosome concordance data of two independent hybrid clone panels.

Original languageEnglish (US)
Pages (from-to)6354-6358
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number14
DOIs
StatePublished - Jul 3 1995
Externally publishedYes

Keywords

  • chromosomal aberrations
  • crosslinking agents
  • genetic complementation
  • irs1SF

ASJC Scopus subject areas

  • Genetics
  • General

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