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Inhibition of nucleosome assembly by the mismatch repair system
Author(s) -
Takahashi Tatsuro,
Taki Kanae,
Higashi Torahiko,
Nakagawa Takuro,
Masukata Hisao
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.491.4
Subject(s) - nucleosome , dna mismatch repair , xenopus , dna , base pair , biology , chromatin , dna replication , genetics , biophysics , microbiology and biotechnology , chemistry , dna repair , gene
The mismatch repair (MMR) system post‐replicatively corrects replication errors such as base‐base mismatches. The MMR reaction begins with recognition of the errors by the MutS complex. MutS and other factors then identify the erroneous newly synthesized strand. The nature of strand discrimination signals in eukaryotes remains elusive, but a gap or 3′‐end of DNA can work as the signal in vitro. Concurrent with the MMR reaction, nucleosomes re‐assemble on the replicated DNA strands. Nucleosome assembly might impede the MMR reaction, for example by obscuring strand discrimination signals. However, how the MMR system deals with nucleosome assembly remains highly unclear. Using Xenopus egg extracts as a vertebrate model system, we investigated functional interaction between the MMR reaction and nucleosome assembly. In the nucleoplasmic extracts of Xenopus eggs, nucleosomes rapidly assemble on naked DNA. Surprisingly, nucleosome assembly was severely inhibited when a base‐base mismatch was present on the DNA molecule. The MutS complex specifically bound to the mismatch‐containing DNA, and this complex was essential for both repair of the mismatch and inhibition of nucleosome assembly. These results suggest that nucleosome assembly at replication error loci is temporally inhibited by a MutS‐dependent mechanism during the MMR reaction. We propose that this mechanism is important for eukaryotic MMR in the context of chromatin.