THE HUMAN XRCC9 GENE CORRECTS CHROMOSOMAL INSTABILITY AND MUTAGEN SENSITIVITIES IN CHO UV40 CELLS

The Chinese hamster ovary (CHO) mutant UV40 cell line is hypersensitiv e to UV and ionizing radiation, simple alkylating agents, and DNA cros s-linking agents. The mutant cells also have a high level of spontaneo us chromosomal aberrations and 3-fold elevated sister chromatid exchan ge. We cloned and sequenced a human cDNA, designated XRCC9, that parti ally corrected the hypersensitivity of UV40 to mitomycin C, cisplatin, ethyl methanesulfonate, UV, and gamma-radiation. The spontaneous chro mosomal aberrations in XRCC9 cDNA transformants wc re almost fully cor rected whereas sister chromatid exchanges were unchanged. The XRCC9 ge nomic sequence was cloned and mapped to chromosome 9p13. The translate d,YRCC9 sequence of 622 amino acids has no similarity with known prote ins, The 2.5-kb, XRCC9 mRNA seen in the parental cells was undetectabl e in UV40 cells, The mRNA levels in testis were up to 10-fold higher c ompared with other human tissues and up to 100-fold higher compared wi th other baboon tissues, XRCC9 is a candidate tumor suppressor gene th at might operate in a postreplication repair or a cell cycle checkpoin t function.