Localization of Genes Involved in DNA Repair on Human Chromosomes by Using Cell Fusion

Stefanini, Miria; Keijzer, W.; Reuser, Arnold; Kessel, Ad Geurts van; Verkerk, T.; Westerveld, A.; Jongkind, J. F.; Bootsma, D.

doi:10.1007/978-1-4757-1117-2_45

Cited by 1 publication

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“…(17) recently reported that a gene on human X chromosome was involved in the fast complementation kinetics of the XP defect. In the present study, the X chromosome was not involved in recovering UV sensitivity in the human-mouse cell hybrids.…”

Section: Resultsmentioning

confidence: 99%

Human chromosome 13 compensates a DNA repair defect in UV-sensitive mouse cells by mouse--human cell hybridization.

Hori¹,

Shiomi²,

Sato³

1983

Proc. Natl. Acad. Sci. U.S.A.

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A human chromosome responsible for excision repair of UV-induced DNA damage has been identified by studying somatic cell hybrids between an UV-sensitive mutant of mouse lymphoma L5178Y cells and normal human lymphocytes. An autosomal recessive mutant, Q31, of complementation group I is deficient in excision repair of UV-induced DNA damage. Somatic cell hybrids between Q31 and human lymphocytes exhibited the same UV resistance as did parental L5178Y cells. In addition, both the levels of UV-induced unscheduled DNA synthesis and chromosomal sensitivity were recovered from the UV-resistant hybrid clones. Segregation of the hybrid cells gave rise to UV-sensitive clones. The segregation of UV sensitivity was not correlated with the loss of human X chromosome. Karyotype analysis of the segregants gave evidence that a gene on human chromosome 13 compensates for UV hypersensitivity of Q31 mutant.DNA repair has been implicated as modulating mutagenesis and carcinogenesis of certain human genetic diseases. For example, somatic cells derived from a xeroderma pigmentosum (XP) patient who has a genetic predisposition to sunlight-induced skin cancer are known to be hypersensitive to the killing effects of UV (1) and significantly more sensitive to UV-induced mutagenesis than are cells from normal individuals (2). Most XP cells are defective in the first step of excision repair of UV-induced DNA damage and fall into seven complementation groups (3-5). However, the genetic basis of phenotypic complementation is not yet clear, and human enzymes responsible for DNA repair in vivo remain to be identified.The chromosome assignment of human gene(s) that function in the DNA repair process is an important approach to understanding the genetic basis of complementation and may provide clues for identifying gene product from specific human chromosomal DNA. Many human genes have been mapped by concordant segregation of specific human chromosomes and specific gene markers in rodent-human cell hybrids. UV-sensitive mutants with DNA repair defects are now available in rodent cell lines (6, 7), and mutants from mouse lymphoma L5178Y cells fall into four complementation groups (8). An autosomal recessive mutant, Q31, of complementation group I (8, 9) is completely deficient in excision repair of UV-induced DNA damage (10). In an attempt to understand the genetic basis of complementation, we have initiated a program of mapping human chromosomes that carry gene(s) which compensate the DNA repair defects of UV-sensitive mouse mutants in mouse-human cell hybrids.In the present study, we examined somatic cell hybrids produced from the fusion between UV-sensitive Q31 cells and normal human lymphocytes. We mapped a gene on human chromosome 13 that appears to compensate for the DNA repair defect of an UV-sensitive mouse mutation, and we report the successful human chromosome mapping of a gene responsible for UV-sensitivity in mammalian cells. MATERIALS AND METHODSCells and Culture Conditions. Mouse lymphoma L5178Y cell line and its UV-sensiti...

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Section: Resultsmentioning

confidence: 99%