A role for RAD54B in homologous recombination in human cells.
In human somatic cells, homologous recombination is a rare event. To facilitate the targeted modification of the genome for research and gene therapy applications, efforts should be directed toward understanding the molecular mechanisms of homologous recombination in human cells. Although human genes homologous to members of the RAD52 epistasis group in yeast have been identified, no genes have been demonstrated to play a role in homologous recombination in human cells. Here, we report that RAD54B plays a critical role in targeted integration in human cells. Inactivation of RAD54B in a colon cancer cell line resulted in severe reduction of targeted integration frequency. Sensitivity to DNA-damaging agents and sister-chromatid exchange were not affected in RAD54B-deficient cells. Parts of these phenotypes were similar to those of Saccharomyces cerevisiae tid1/rdh54 mutants, suggesting that RAD54B may be a human homolog of TID1/RDH54. In yeast, TID1/RDH54 acts in the recombinational repair pathway via roles partially overlapping those of RAD54. Our findings provide the first genetic evidence that the mitotic recombination pathway is functionally conserved from yeast to humans.
Miyagawa
Kiyoshi
K
Department of Molecular Pathology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. miyag@hiroshima-u.ac.jp
Tsuruga
Takanori
T
Kinomura
Aiko
A
Usui
Kiyomi
K
Katsura
Mari
M
Tashiro
Satoshi
S
Mishima
Hiromu
H
Tanaka
Kozo
K
D001483:Base Sequence; D002455:Cell Division / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics; D004265:DNA Helicases; D045643:DNA Repair Enzymes; D026942:DNA Topoisomerases; D004273:DNA, Neoplasm / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics; D018390:Gene Targeting; D005800:Genes, Fungal; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D012854:Sister Chromatid Exchange; D013045:Species Specificity; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D005656:Fungal Proteins; D009687:Nuclear Proteins; C491221:RAD54B protein, human; D029701:Saccharomyces cerevisiae Proteins; C075468:RAD54 protein, S cerevisiae; D004265:DNA Helicases; D026942:DNA Topoisomerases; C541336:RDH54 protein, S cerevisiae; D045643:DNA Repair Enzymes