RRC ID 19712
著者 Zaratiegui M, Vaughn MW, Irvine DV, Goto D, Watt S, Bähler J, Arcangioli B, Martienssen RA.
タイトル CENP-B preserves genome integrity at replication forks paused by retrotransposon LTR.
ジャーナル Nature
Abstract Centromere-binding protein B (CENP-B) is a widely conserved DNA binding factor associated with heterochromatin and centromeric satellite repeats. In fission yeast, CENP-B homologues have been shown to silence long terminal repeat (LTR) retrotransposons by recruiting histone deacetylases. However, CENP-B factors also have unexplained roles in DNA replication. Here we show that a molecular function of CENP-B is to promote replication-fork progression through the LTR. Mutants have increased genomic instability caused by replication-fork blockage that depends on the DNA binding factor switch-activating protein 1 (Sap1), which is directly recruited by the LTR. The loss of Sap1-dependent barrier activity allows the unhindered progression of the replication fork, but results in rearrangements deleterious to the retrotransposon. We conclude that retrotransposons influence replication polarity through recruitment of Sap1 and transposition near replication-fork blocks, whereas CENP-B counteracts this activity and promotes fork stability. Our results may account for the role of LTR in fragile sites, and for the association of CENP-B with pericentromeric heterochromatin and tandem satellite repeats.
巻・号 469(7328)
ページ 112-5
公開日 2011-1-6
DOI 10.1038/nature09608
PII nature09608
PMID 21151105
PMC PMC3057531
MeSH Centromere Protein B / deficiency Centromere Protein B / genetics Centromere Protein B / metabolism* Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism Conserved Sequence / genetics DNA Damage / genetics DNA Replication / genetics* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Genome, Fungal / genetics* Genomic Instability / genetics* Recombination, Genetic Retroelements / genetics* Schizosaccharomyces / genetics* Schizosaccharomyces / metabolism Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism Terminal Repeat Sequences / genetics*
IF 42.779
引用数 59
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
酵母 FY11012 FY11110