Triplet Repeats Form Secondary Structures That Escape DNA Repair in Yeast

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1999 Feb 17

PMID 9990053

Citations 81

Authors

H Moore

P W Greenwell

C P Liu

N Arnheim

T D Petes

Affiliations

Soon will be listed here.

Abstract

Several human neurodegenerative diseases result from expansion of CTG/CAG or CGG/CCG triplet repeats. The finding that single-stranded CNG repeats form hairpin-like structures in vitro has led to the hypothesis that DNA secondary structure formation is an important component of the expansion mechanism. We show that single-stranded DNA loops containing 10 CTG/CAG or CGG/CCG repeats are inefficiently repaired during meiotic recombination in Saccharomyces cerevisiae. Comparisons of the repair of DNA loops with palindromic and nonpalindromic sequences suggest that this inefficient repair reflects the ability of these sequences to form hairpin structures in vivo.

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References

Sinden R, Wells R . DNA structure, mutations, and human genetic disease. Curr Opin Biotechnol. 1992; 3(6):612-22. DOI: 10.1016/0958-1669(92)90005-4. View

Detloff P, White M, Petes T . Analysis of a gene conversion gradient at the HIS4 locus in Saccharomyces cerevisiae. Genetics. 1992; 132(1):113-23. PMC: 1205110. DOI: 10.1093/genetics/132.1.113. View

Bollag R, Elwood D, Tobin E, Godwin A, Liskay R . Formation of heteroduplex DNA during mammalian intrachromosomal gene conversion. Mol Cell Biol. 1992; 12(4):1546-52. PMC: 369596. DOI: 10.1128/mcb.12.4.1546-1552.1992. View

Perkins D . Biochemical Mutants in the Smut Fungus Ustilago Maydis. Genetics. 1949; 34(5):607-26. PMC: 1209467. DOI: 10.1093/genetics/34.5.607. View

Nag D, Petes T . Seven-base-pair inverted repeats in DNA form stable hairpins in vivo in Saccharomyces cerevisiae. Genetics. 1991; 129(3):669-73. PMC: 1204734. DOI: 10.1093/genetics/129.3.669. View

Stapleton A, Petes T . The Tn3 beta-lactamase gene acts as a hotspot for meiotic recombination in yeast. Genetics. 1991; 127(1):39-51. PMC: 1204310. DOI: 10.1093/genetics/127.1.39. View

Nag D, Petes T . Genetic evidence for preferential strand transfer during meiotic recombination in yeast. Genetics. 1990; 125(4):753-61. PMC: 1204101. DOI: 10.1093/genetics/125.4.753. View

Nag D, White M, Petes T . Palindromic sequences in heteroduplex DNA inhibit mismatch repair in yeast. Nature. 1989; 340(6231):318-20. DOI: 10.1038/340318a0. View

Weiss U, Wilson J . Repair of single-stranded loops in heteroduplex DNA transfected into mammalian cells. Proc Natl Acad Sci U S A. 1987; 84(6):1619-23. PMC: 304487. DOI: 10.1073/pnas.84.6.1619. View

10.

Struhl K, Stinchcomb D, Scherer S, Davis R . High-frequency transformation of yeast: autonomous replication of hybrid DNA molecules. Proc Natl Acad Sci U S A. 1979; 76(3):1035-9. PMC: 383183. DOI: 10.1073/pnas.76.3.1035. View

11.

Scherer S, Davis R . Replacement of chromosome segments with altered DNA sequences constructed in vitro. Proc Natl Acad Sci U S A. 1979; 76(10):4951-5. PMC: 413056. DOI: 10.1073/pnas.76.10.4951. View

12.

Streisinger G, Okada Y, Emrich J, Newton J, Tsugita A, Terzaghi E . Frameshift mutations and the genetic code. This paper is dedicated to Professor Theodosius Dobzhansky on the occasion of his 66th birthday. Cold Spring Harb Symp Quant Biol. 1966; 31:77-84. DOI: 10.1101/sqb.1966.031.01.014. View

13.

Boeke J, Lacroute F, Fink G . A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance. Mol Gen Genet. 1984; 197(2):345-6. DOI: 10.1007/BF00330984. View

14.

Yu A, Dill J, Mitas M . The purine-rich trinucleotide repeat sequences d(CAG)15 and d(GAC)15 form hairpins. Nucleic Acids Res. 1995; 23(20):4055-7. PMC: 307342. DOI: 10.1093/nar/23.20.4055. View

15.

Yu A, Dill J, Wirth S, Huang G, Lee V, Haworth I . The trinucleotide repeat sequence d(GTC)15 adopts a hairpin conformation. Nucleic Acids Res. 1995; 23(14):2706-14. PMC: 307095. DOI: 10.1093/nar/23.14.2706. View

16.

Kang S, Jaworski A, Ohshima K, Wells R . Expansion and deletion of CTG repeats from human disease genes are determined by the direction of replication in E. coli. Nat Genet. 1995; 10(2):213-8. DOI: 10.1038/ng0695-213. View

17.

Mitas M, Yu A, Dill J, Kamp T, Chambers E, Haworth I . Hairpin properties of single-stranded DNA containing a GC-rich triplet repeat: (CTG)15. Nucleic Acids Res. 1995; 23(6):1050-9. PMC: 306804. DOI: 10.1093/nar/23.6.1050. View

18.

Gacy A, Goellner G, Juranic N, Macura S, McMurray C . Trinucleotide repeats that expand in human disease form hairpin structures in vitro. Cell. 1995; 81(4):533-40. DOI: 10.1016/0092-8674(95)90074-8. View

19.

Fan Q, Xu F, Petes T . Meiosis-specific double-strand DNA breaks at the HIS4 recombination hot spot in the yeast Saccharomyces cerevisiae: control in cis and trans. Mol Cell Biol. 1995; 15(3):1679-88. PMC: 230392. DOI: 10.1128/MCB.15.3.1679. View

20.

Richards R, Sutherland G . Simple repeat DNA is not replicated simply. Nat Genet. 1994; 6(2):114-6. DOI: 10.1038/ng0294-114. View