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Palindromic protection

Palindromes allow yeast cells lacking telomeres and Exo1 (arrows) to replicate. LYDALL/CSHL

Research from Laura Maringele and David Lydall (University of Newcastle, UK) shows that yeast find a way to survive in the absence of telomeres. By forming large palindromes at chromosome ends, yeast mutants proliferate for many generations despite genomic instability, possibly becoming the yeast equivalent of cancer cells.

Chromosomes are progressively eroded with each cell cycle if they are not protected by telomeres, in part because the DNA replication machinery cannot copy the ends of linear DNA. Telomeres are maintained by telomerase or, when telomerase is compromised, by recombination. Maringele and Lydall now uncover a pathway to prevent chromosome shortening that is independent of both telomerase and recombination.

This pathway was seen in yeast mutants lacking the Exo1 nuclease. These mutants escape the cell cycle checkpoints that are normally activated by the loss of telomeres, probably because the mutants generate less checkpoint-activating ssDNA at unprotected ends. Further replication of these mutants was expected to cause death from loss of essential telomere-proximal genes, but many survivors were viable for thousands of generations.

Chromosomes in the surviving lines were shortened, but essential genes were protected by large mirror image duplications called palindromes. Palindromes were consistently found to originate at short inverted repeats (IRs). Short IRs have been suggested by others to initiate palindrome formation through a DNA repair mechanism. The extra hundreds of kilobases of DNA that the authors found at chromosome ends should protect chromosomes for thousands of generations. "You can keep chewing up the ends of palindromes until you get close to essential genes, and then repeat," says Lydall.

Mammalian somatic cells, which are low in both telomerase and recombination, might also escape checkpoint controls at the end of their replicative life span due to low levels of Exo1 (or equivalent nucleases) and gain immortality via palindromes. Whether palindromes are formed in precancerous cells and aid in malignancy remains to be seen.

Reference:

Maringele, L., and D. Lydall. 2004. Genes Dev. 18:2663–2675.[Abstract/Free Full Text]

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article Full Text (PDF, 589K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                            What's this?