Towards understanding the mechanisms of palindromic gene amplification.
Alison Rattray, Anne Welcker, Brenda Shafer, Jeffrey Strathern
GRCBL, NCI-FCRDC, PO Box B, Frederick, MD, 21702, USA
DNA sequences containing long adjacent inverted repeats (palindromes) are thought to be important in the initiation and propagation of a class of gene amplification events that are often associated with tumorigenesis. Several years ago we showed that the introduction of a double-strand break between chromosomally located inverted repeats in Saccharomyces cerevisiae could result in a high degree if palindrome formation if the cells were deficient in mre11, rad50 or sae2 (Rattray et al, 2001 Genetics 158: 109). We present further characterization of the genetic requirements for palindrome formation and maintenance. Taking advantage of the ability to stably maintain the palindromes in sae2 deficient yeast cells, we were able to develop the methodology to sequence the palindromic junctions. Our data indicates that the palindromes are formed by intra-strand annealing between extremely short (4-6 bp) inverted repeats, which can then serve to prime DNA synthesis. These data suggest that almost any DNA sequence region is capable of initiating a palindromic gene amplification event.
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