CONSTRUCTION OF A 2.8-MEGABASE YEAST ARTIFICIAL CHROMOSOME CONTIG AND CLONING OF THE HUMAN METHYLTHIOADENOSINE PHOSPHORYLASE GENE FROM THE TUMOR-SUPPRESSOR REGION ON 9P21

被引：90

作者：

OLOPADE, OI ^{[1
]}

POMYKALA, HM ^{[1
]}

HAGOS, F ^{[1
]}

SVEEN, LW ^{[1
]}

ESPINOSA, R ^{[1
]}

DREYLING, MH ^{[1
]}

GURSKY, S ^{[1
]}

STADLER, WM ^{[1
]}

LEBEAU, MM ^{[1
]}

BOHLANDER, SK ^{[1
]}

机构：

[1] UNIV CHICAGO,PRITZKER SCH MED,CANC RES CTR,CHICAGO,IL 60637

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1995年 / 92卷 / 14期

关键词：

CHROMOSOMAL LOSS; PURINE NUCLEOSIDE PHOSPHORYLASE; ENZYME DEFICIENCY; CDKN2; GENE;

D O I：

10.1073/pnas.92.14.6489

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Many human malignant cells lack methylthioadenosine phosphorylase (MTAP) enzyme activity, The gene (MTAP) encoding this enzyme was previously mapped to the short arm of chromosome 9, band p21-22, a region that is frequently deleted in multiple tumor types. To clone candidate tumor suppressor genes from the deleted region on 9p21-22, we have constructed a long-range physical map of 2.8 megabases for 9p21 by using overlapping yeast artificial chromosome and cosmid clones. This map includes the type I IFN gene cluster, the recently identified candidate tumor suppressor genes CDKN2 (p16(INK4A)) and CDKN2B (p15(INK4B)), and several CpG islands, In addition, we have identified other transcription units within the yeast artificial chromosome contig. Sequence analysis of a 2,5-kb cDNA clone isolated from a CpG island that maps between the IFN genes and CDKN2 reveals a predicted open reading frame of 283 amino acids followed by 1302 nucleotides of 3' untranslated sequence. This gene is evolutionarily conserved and shows significant amino acid homologies to mouse and human purine nucleoside phosphorylases and to a hypothetical 25.8 kDa protein in the pet gene (coding for cytochrome bc(1) complex) region of Rhodospirillum rubrum. The location, expression pattern, and nucleotide sequence of this gene suggest that it codes for the MTAP enzyme.

引用

页码：6489 / 6493

页数：5

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