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

M. Zaratiegui; M.W. Vaughn; D.V. Irvine; D.B. Goto; S. Watt; J. Bähler; B. Arcangioli; R.A. Martienssen

doi:10.1038/nature09608

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

Journal article

Peer reviewed

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

M. Zaratiegui, M.W. Vaughn, D.V. Irvine, D.B. Goto, S. Watt, J. Bähler, B. Arcangioli and R.A. Martienssen

Nature, Vol.469(7328), pp.112-115

2011

DOI: https://doi.org/10.1038/nature09608

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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.

Details

Title: CENP-B preserves genome integrity at replication forks paused by retrotransposon LTR
Authors/Creators: M. Zaratiegui (Author/Creator) - Cold Spring Harbor Laboratory
M.W. Vaughn (Author/Creator) - Cold Spring Harbor Laboratory
D.V. Irvine (Author/Creator) - Cold Spring Harbor Laboratory
D.B. Goto (Author/Creator) - Cold Spring Harbor Laboratory
S. Watt (Author/Creator) - The University of Texas at Austin
J. Bähler (Author/Creator) - Department of Genetics, University College London, Evolution & Environment, and UCL Cancer Institute, Darwin Building, London, UK
B. Arcangioli (Author/Creator) - Institut Pasteur
R.A. Martienssen (Author/Creator) - Cold Spring Harbor Laboratory
Publication Details: Nature, Vol.469(7328), pp.112-115
Publisher: Nature Publishing Group
Identifiers: 991005544307707891
Copyright: © 2010 Macmillan Publishers Limited.
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.152 Molecular & Cell Biology - DNA Damage; 1.152.257 Repair Mechanisms
Web Of Science research areas: Biochemistry & Molecular Biology
ESI research areas: Molecular Biology & Genetics