Structural and functional conservation of the human homolog of the Schizosaccharomyces pombe rad2 gene, which is required for chromosome segregation and recovery from DNA damage.
The rad2 mutant of Schizosaccharomyces pombe is sensitive to UV irradiation and deficient in the repair of UV damage. In addition, it has a very high degree of chromosome loss and/or nondisjunction. We have cloned the rad2 gene and have shown it to be a member of the Saccharomyces cerevisiae RAD2/S. pombe rad13/human XPG family. Using degenerate PCR, we have cloned the human homolog of the rad2 gene. Human cDNA has 55% amino acid sequence identity to the rad2 gene and is able to complement the UV sensitivity of the rad2 null mutant. We have thus isolated a novel human gene which is likely to be involved both in controlling the fidelity of chromosome segregation and in the repair of UV-induced DNA damage. Its involvement in two fundamental processes for maintaining chromosomal integrity suggests that it is likely to be an important component of cancer avoidance mechanisms.
Murray
J M
JM
Department of Biochemistry, Sussex University, Falmer, United Kingdom.
Tavassoli
M
M
al-Harithy
R
R
Sheldrick
K S
KS
Lehmann
A R
AR
Carr
A M
AM
Watts
F Z
FZ
D000595:Amino Acid Sequence; D001483:Base Sequence; D015825:Chromosomes, Fungal / Q000502:physiology*; D003001:Cloning, Molecular; D004249:DNA Damage; D004271:DNA, Fungal / Q000235:genetics / Q000528:radiation effects*; D004268:DNA-Binding Proteins; D004307:Dose-Response Relationship, Radiation; D004706:Endodeoxyribonucleases / Q000235:genetics; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics*; D005720:Gamma Rays; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D006801:Humans; D008969:Molecular Sequence Data; D015183:Restriction Mapping; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000235:genetics* / Q000528:radiation effects; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014466:Ultraviolet Rays
D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; C073998:RAD2 protein, S cerevisiae; D004706:Endodeoxyribonucleases