Expansion and length-dependent fragility of CTG repeats in yeast

被引：343

作者：

Freudenreich, CH ^{[1
]}

Kantrow, SM ^{[1
]}

Zakian, VA ^{[1
]}

机构：

[1] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA

来源：

SCIENCE | 1998年 / 279卷 / 5352期

关键词：

D O I：

10.1126/science.279.5352.853

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：

Expansion of DNA trinucleotide repeats (TNRs) is the causative mutation in a growing number of human genetic diseases. Large expansions of a CTG tract were obtained and shown by genetic and physical assays to be length-dependent sites of chromosome breakage in Saccharomyces cerevisiae. Deletion of RAD27, which encodes a nuclease involved in Okazaki fragment processing, caused length-dependent destabilization of CTG tracts and a substantial increase in expansion frequency. The genetic assay described here can be used to evaluate other factors that induce TNR expansion or chromosome fragility in humans.

引用

页码：853 / 856

页数：4

共 34 条

[1] Instability of the expanded (CTG)(n) repeats in the myotonin protein kinase gene in cultured lymphoblastoid cell lines from patients with myotonic dystrophy [J].

Ashizawa, T ;

Monckton, DG ;

Vaishnav, S ;

Patel, BJ ;

Voskova, A ;

Caskey, CT .

GENOMICS, 1996, 36 (01) :47-53

[2] Trinucleotide repeat expansion and human disease [J].

Ashley, CT ;

Warren, ST .

ANNUAL REVIEW OF GENETICS, 1995, 29 :703-728

[3] A SIMPLE AND EFFICIENT METHOD FOR DIRECT GENE DELETION IN SACCHAROMYCES-CEREVISIAE [J].

BAUDIN, A ;

OZIERKALOGEROPOULOS, O ;

DENOUEL, A ;

LACROUTE, F ;

CULLIN, C .

NUCLEIC ACIDS RESEARCH, 1993, 21 (14) :3329-3330

[4] Deletions at stalled replication forks occur by two different pathways [J].

Bierne, H ;

Ehrlich, SD ;

Michel, B .

EMBO JOURNAL, 1997, 16 (11) :3332-3340

[5] CHARACTERIZATION OF YEAST ARTIFICIAL CHROMOSOMES FROM PLASMODIUM-FALCIPARUM - CONSTRUCTION OF A STABLE, REPRESENTATIVE LIBRARY AND CLONING OF TELOMERIC DNA FRAGMENTS [J].

DEBRUIN, D ;

LANZER, M ;

RAVETCH, JV .

GENOMICS, 1992, 14 (02) :332-339

[6] Stability of a CTG/CAG trinucleotide repeat in yeast is dependent on its orientation in the genome [J].

Freudenreich, CH ;

Stavenhagen, JB ;

Zakian, VA .

MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (04) :2090-2098

[7] IMPROVED METHOD FOR HIGH-EFFICIENCY TRANSFORMATION OF INTACT YEAST-CELLS [J].

GIETZ, D ;

STJEAN, A ;

WOODS, RA ;

SCHIESTL, RH .

NUCLEIC ACIDS RESEARCH, 1992, 20 (06) :1425-1425

[8] Repeat expansion - All in a flap? [J].

Gordenin, DA ;

Kunkel, TA ;

Resnick, MA .

NATURE GENETICS, 1997, 16 (02) :116-118

[9] FUNCTIONAL DOMAINS WITHIN FEN-1 AND RAD2 DEFINE A FAMILY OF STRUCTURE-SPECIFIC ENDONUCLEASES - IMPLICATIONS FOR NUCLEOTIDE EXCISION-REPAIR [J].

HARRINGTON, JJ ;

LIEBER, MR .

GENES & DEVELOPMENT, 1994, 8 (11) :1344-1355

[10] SEQUENTIAL FUNCTION OF GENE PRODUCTS RELATIVE TO DNA-SYNTHESIS IN YEAST-CELL CYCLE [J].

HARTWELL, LH .

JOURNAL OF MOLECULAR BIOLOGY, 1976, 104 (04) :803-817

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