Instability of repetitive DNA sequences: The role of replication in multiple mechanisms

Department of Biology and Rosenstiel Basic Medical Sciences Research, Center MS029, Brandeis University, 415 South Street, Waltham, MA 02454-9110

Abstract

Rearrangements between tandem sequence homologies of various lengths are a major source of genomic change and can be deleterious to the organism. These rearrangements can result in either deletion or duplication of genetic material flanked by direct sequence repeats. Molecular genetic analysis of repetitive sequence instability in Escherichia coli has provided several clues to the underlying mechanisms of these rearrangements. We present evidence for three mechanisms of RecA-independent sequence rearrangements: simple replication slippage, sister-chromosome exchange-associated slippage, and single-strand annealing. We discuss the constraints of these mechanisms and contrast their properties with RecA-dependent homologous recombination. Replication plays a critical role in the two slipped misalignment mechanisms, and difficulties in replication appear to trigger rearrangements via all these mechanisms.

Footnotes

↵ * Present address: Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138.
↵ † To whom reprint requests should be addressed. E-mail: lovett{at}brandeis.edu.
This paper results from the National Academy of Sciences colloquium, “Links Between Recombination and Replication: Vital Roles of Recombination,” held November 10–12, 2000, in Irvine, CA.
Abbreviations:

ssDNA,

single-strand DNA;

DSB,

double-strand break;

SCE,

sister-chromosome exchange