HRad17, a human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, is overexpressed in colon carcinoma.
Using the palindromic PCR-cDNA display method, we have cloned a novel gene overexpressed by human colon carcinoma relative to normal colon. Among normal tissues examined, only testis expresses it at a high level. Sequence analysis revealed its extensive homology with checkpoint genes rad17 of Schizosaccharomyces pombe and RAD24 of Saccharomyces cerevisiae. This novel gene designated as hRad17 is localized to chromosome 5q12,13.1, a region known to be deleted in a variety of human cancers. Promoter region and one pseudogene of hRad17 have been identified. Whereas the increased expression of hRad17 by human colon carcinomas may be related to the known resistance of these cells to DNA-damaging agents during therapy, the deletion of hRad17 in a variety of cancers may predispose them to increased rate of mutation and heightened sensitivity to DNA-damaging agents, including radiation and anticancer drugs.
Bao
S
S
Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts 02115, USA.
Chang
M S
MS
Auclair
D
D
Sun
Y
Y
Wang
Y
Y
Wong
W K
WK
Zhang
J
J
Liu
Y
Y
Qian
X
X
Sutherland
R
R
Magi-Galluzi
C
C
Weisberg
E
E
Cheng
E Y
EY
Hao
L
L
Sasaki
H
H
Campbell
M S
MS
Kraeft
S K
SK
Loda
M
M
Lo
K M
KM
Chen
L B
LB
D000818:Animals; D001483:Base Sequence; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics*; D002522:Chlorocebus aethiops / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D003001:Cloning, Molecular; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000235:genetics*; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D005796:Genes; D005800:Genes, Fungal; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011544:Pseudogenes / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins; D013737:Testis / Q000378:metabolism
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C501395:RAD17 protein, S cerevisiae; C088385:RAD24 protein, S cerevisiae; C113575:Rad17 protein, human; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C501114:rad24 protein, S pombe