TY - JOUR
T1 - Formation of circular amplifications in Saccharomyces cerevisiae by a breakage-fusion-bridge mechanism
AU - Zheng, Ningjia
AU - Monckton, Darren G.
AU - Wilson, Gene
AU - Hagemeister, Fredrick
AU - Chakraborty, Ranajit
AU - Connor, Thomas H.
AU - Siciliano, Michael J.
AU - Meistrich, Marvin L.
PY - 2000
Y1 - 2000
N2 - Primary gene amplification, the mutation from one gene copy per genome to two or more copies per genome, is a major mechanism of oncogene overexpression in human cancers. Analysis of the structures of amplifications can provide important evidence about the mechanism of amplification formation. We report here the analysis of the structures of four independent spontaneous circular amplifications of ADH4:CUP1 in the yeast Saccharomyces cerevisiae. The structures of all four amplifications are consistent with their formation by a breakage-fusion-bridge (BFB) mechanism. All four of these amplifications include a centromere as predicted by the BFB model. All four of the amplifications have a novel joint located between the amplified DNA and the telomere, which results in a dicentric chromosome, and is adjacent to all the copies of the amplified DNA as predicted by the BFB model. In addition we demonstrated that two of the amplifications contain most of chromosome VII in an unrearranged form in a 1:1 ratio with the normal copy of chromosome VII, again consistent with the predictions of the BFB model. Finally, all four amplifications are circular, one stable endpoint for molecules after breakagefusion-bridge. (C) 2000 Wiley-Liss, Inc.
AB - Primary gene amplification, the mutation from one gene copy per genome to two or more copies per genome, is a major mechanism of oncogene overexpression in human cancers. Analysis of the structures of amplifications can provide important evidence about the mechanism of amplification formation. We report here the analysis of the structures of four independent spontaneous circular amplifications of ADH4:CUP1 in the yeast Saccharomyces cerevisiae. The structures of all four amplifications are consistent with their formation by a breakage-fusion-bridge (BFB) mechanism. All four of these amplifications include a centromere as predicted by the BFB model. All four of the amplifications have a novel joint located between the amplified DNA and the telomere, which results in a dicentric chromosome, and is adjacent to all the copies of the amplified DNA as predicted by the BFB model. In addition we demonstrated that two of the amplifications contain most of chromosome VII in an unrearranged form in a 1:1 ratio with the normal copy of chromosome VII, again consistent with the predictions of the BFB model. Finally, all four amplifications are circular, one stable endpoint for molecules after breakagefusion-bridge. (C) 2000 Wiley-Liss, Inc.
KW - ADH4
KW - Breakage-fusion-bridge
KW - Gene amplification
KW - Saccharomyces cerevisiae
UR - http://www.scopus.com/inward/record.url?scp=0033771203&partnerID=8YFLogxK
U2 - 10.1002/1098-2280(2000)36:2<113::AID-EM5>3.0.CO;2-T
DO - 10.1002/1098-2280(2000)36:2<113::AID-EM5>3.0.CO;2-T
M3 - Article
C2 - 11013409
AN - SCOPUS:0033771203
SN - 0893-6692
VL - 36
SP - 113
EP - 120
JO - Environmental and Molecular Mutagenesis
JF - Environmental and Molecular Mutagenesis
IS - 2
ER -