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PMID: 12065432 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Instability of the human minisatellite CEB1 in rad27Delta and dna2-1 replication-deficient yeast cells.

The EMBO journal ·Vol. 21 ·No. 12 ·2002-06-17 ·Pages 3201-11

Lopes J, Debrauwère H, Buard J, Nicolas A

Abstract

Convergent studies in human and yeast model systems have shown that some minisatellite loci are relatively stable in somatic cells but not in the germline, and little is known about the mechanism(s) that can destabilize them. Unlike microsatellite sequences, mini satellites are not destabilized by mismatch repair mutations. We report here that the absence of Rad27 and Dna2 functions but not RNase H(35) or Exo1, which play an essential role in the processing of Okazaki fragments during replication, destabilize the human minisatellite CEB1 in mitotically growing Saccharomyces cerevisiae cells, up to 14% per generation in rad27Delta cells. Analysis using minisatellite variant repeat mapping by polymerase chain reaction of the internal structure of 17 variants reveals that the majority of rearrangements in rad27Delta cells are extremely complex contraction events that contain deletions, often accompanied by duplications of motif unit. Altogether, these results suggest that the improperly processed 5' flap structures that accumulate when replication is impaired can act as a potent stimulator of minisatellite destabilization and can provoke an unexpectedly broad range of mutagenic events. This replication-dependent phenomenon differs from the recombination-induced instability in yeast meiotic cells.

MeSH Terms
Adenosine Triphosphatases/genetics,metabolism Alleles Base Sequence DNA/genetics,metabolism DNA Helicases/genetics,metabolism DNA Repair DNA Replication/genetics Endodeoxyribonucleases/genetics,metabolism Flap Endonucleases Humans Minisatellite Repeats/genetics Models, Genetic Molecular Sequence Data Polymerase Chain Reaction/methods Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae Proteins Temperature
Chemicals
Okazaki fragments Saccharomyces cerevisiae Proteins DNA Endodeoxyribonucleases Flap Endonucleases FEN1 protein, human RAD27 protein, S cerevisiae Adenosine Triphosphatases DNA Helicases DNA2 protein, S cerevisiae
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lopes Judith
Institut Curie, Section de Recherche, CNRS UMR144, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
Debrauwère Hélène
Buard Jérôme
Nicolas Alain
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdf310
Published
2002-06-17
Pages
3201-11
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125388
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdf310 PMC Full Text View journal details
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