The human XRCC9 gene corrects chromosomal instability and mutagen sensitivities in CHO UV40 cells

Nan Liu, Jane E. Lamerdin, James D. Tucker, Zi Q. Zhou, Christi A. Walter, Joanna S. Albala, David B. Busch, Larry H. Thompson

Research output: Contribution to journalArticle

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Abstract

The Chinese hamster ovary (CHO) mutant UV40 cell line is hypersensitive to UV and ionizing radiation, simple alkylating agents, and DNA cross- linking agents. The mutant cells also have a high level of spontaneous chromosomal aberrations and 3-fold elevated sister chromatid exchange. We cloned and sequenced a human cDNA, designated XRCC9, that partially corrected the hypersensitivity of UV40 to mitomycin C, cisplatin, ethyl methanesulfonate, UV, and γ-radiation. The spontaneous chromosomal aberrations in XRCC9 cDNA transformants were almost fully corrected whereas sister chromatid exchanges were unchanged. The XRCC9 genomic sequence was cloned and mapped to chromosome 9p13. The translated XRCC9 sequence of 622 amino acids has no similarity with known proteins. The 2.5-kb XRCC9 mRNA seen in the parental cells was undetectable in UV40 cells. The mRNA levels in testis were up to 10-fold higher compared with other human tissues and up to 100-fold higher compared with other baboon tissues. XRCC9 is a candidate tumor suppressor gene that might operate in a postreplication repair or a cell cycle checkpoint function.

Original languageEnglish (US)
Pages (from-to)9232-9237
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number17
DOIs
StatePublished - Aug 19 1997
Externally publishedYes

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Chromosomal Instability
Mutagens
Cricetulus
Ovary
Sister Chromatid Exchange
Chromosome Aberrations
Complementary DNA
Ethyl Methanesulfonate
Genes
Messenger RNA
Papio
Alkylating Agents
Mitomycin
Cell Cycle Checkpoints
Ionizing Radiation
Tumor Suppressor Genes
Cisplatin
Testis
Amino Acid Sequence
Hypersensitivity

Keywords

  • Chromosome aberrations
  • DNA repair
  • Radiation sensitivity
  • Sister chromatid exchange

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The human XRCC9 gene corrects chromosomal instability and mutagen sensitivities in CHO UV40 cells. / Liu, Nan; Lamerdin, Jane E.; Tucker, James D.; Zhou, Zi Q.; Walter, Christi A.; Albala, Joanna S.; Busch, David B.; Thompson, Larry H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 17, 19.08.1997, p. 9232-9237.

Research output: Contribution to journalArticle

Liu, Nan ; Lamerdin, Jane E. ; Tucker, James D. ; Zhou, Zi Q. ; Walter, Christi A. ; Albala, Joanna S. ; Busch, David B. ; Thompson, Larry H. / The human XRCC9 gene corrects chromosomal instability and mutagen sensitivities in CHO UV40 cells. In: Proceedings of the National Academy of Sciences of the United States of America. 1997 ; Vol. 94, No. 17. pp. 9232-9237.
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