PMID:21151105

Citation	Zaratiegui, M, Vaughn, MW, Irvine, DV, Goto, D, Watt, S, Bähler, J, Arcangioli, B and Martienssen, RA (2011) CENP-B preserves genome integrity at replication forks paused by retrotransposon LTR. Nature 469:112-5
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.
Links	PubMed PMC3057531 Online version:10.1038/nature09608
Keywords	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
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
SCHPO:ABP1		GO:2000105 : positive regulation of DNA-dependent DNA replication	ECO:0000315:		P		Figure 1	complete
SCHPO:SAP1		GO:0008156: negative regulation of DNA replication	ECO:0000315:		P		Fig. 1	complete
SCHPO:CBH1		GO:2000105: positive regulation of DNA-dependent DNA replication	ECO:0000315:		P		Fig. 1	complete

References

See Help:References for how to manage references in GONUTS.