Palindromic DNA and genome stability: Further studies Conference Paper


Authors: Lewis, S.; Akgun, E.; Jasin, M.
Title: Palindromic DNA and genome stability: Further studies
Conference Title: Molecular Strategies in Biological Evolution
Abstract: Unusual DNA structures promote genetic instability. One such example is hairpin DNA, which can form from palindromic sequences and triplet repeats, and is also a characteristic intermediate in V(D)J recombination.We previously found that a large 15.3-kb palindrome that was introduced as a transgene into the mouse germline was highly unstable.Although it could be transmitted, the transgene was found to be rearranged in up to 56% of the progeny, and rearrangement events often involved deletion at the center of symmetry, Here, the fine structure of centrally deleted palindromes was sampled by analysis of recombinant junctions isolated from testes DNA, providing further evidence for a model, previously proposed, that accounts for such deletions on the basis of a hairpin-tip nicking activity. In addition to central deletions, gene conversion events were also elevated in the transgenic palindrome. We have now analyzed instability in two mouse sublines in which (as a result of inversion) the transgenic palindrome had been shortened to 4.2 kb.In these sublines, the transgene was still subject to both rearrangement and gene conversion events at a high frequency, similar to the original 15.3-kb palindrome. Recombination was not limited to the sequences constituting the inverted repeat, but was seen to include sequences lying outside the palindrome. As discussed, the salient feature in all of these observations, a high level of genetic change associated with palindromic DNA, underscores the significance of hairpin DNA and hairpin-tip nicking in genome stability.
Keywords: mice; amplification; yeast; resolution; sequences; mammalian-cells; repeats; locus
Journal Title Annals of the New York Academy of Sciences
Volume: 870
Conference Dates: 1998 Jun 27-29
Conference Location: New York, NY
ISBN: 0077-8923
Publisher: John Wiley & Sons  
Location: New York
Date Published: 1999-05-18
Start Page: 45
End Page: 57
Language: English
ACCESSION: WOS:000081585400005
PROVIDER: wos
PUBMED: 10415472
DOI: 10.1111/j.1749-6632.1999.tb08864.x
Notes: Chapter in "Molecular Strategies in Biological Evolution" (ISBN: 9781573311922) -- Article; Proceedings Paper -- Conference on Molecular Strategies in Biological Evolution that took place 1998 Jun 27-29 in New York, NY -- Source: Wos
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  1. Ercan Akgun
    4 Akgun
  2. Maria Jasin
    250 Jasin