CENP-B preserves genome integrity at replication forks paused by retrotransposon LTR.

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.

• Authors: Mikel Zaratiegui, Matthew W Vaughn, Danielle V Irvine, Derek Goto, Stephen Watt, Jürg Bähler, Benoit Arcangioli, Robert A Martienssen
• Journal: Nature (Nature) Vol. 469 Issue 7328 Pg. 112-5 (Jan 06 2011) ISSN: 1476-4687 [Electronic] England
• PMID: 21151105 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cbh1 protein, S pombe
• Cbh2 protein, S pombe
• Centromere Protein B
• Chromosomal Proteins, Non-Histone
• DNA-Binding Proteins
• Retroelements
• Sap1 protein, S pombe
• Schizosaccharomyces pombe Proteins
• cbp1 protein, S pombe

Topics

• Centromere Protein B (deficiency, genetics, metabolism)
• Chromosomal Proteins, Non-Histone (genetics, metabolism)
• Conserved Sequence (genetics)
• DNA Damage (genetics)
• DNA Replication (genetics)
• DNA-Binding Proteins (genetics, metabolism)
• Genome, Fungal (genetics)
• Genomic Instability (genetics)
• Recombination, Genetic
• Retroelements (genetics)
• Schizosaccharomyces (genetics, metabolism)
• Schizosaccharomyces pombe Proteins (genetics, metabolism)
• Terminal Repeat Sequences (genetics)