DNA Copy-Number Control through Inhibition of Replication Fork Progression
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Orr-Weaver_DNA copy.pdf
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2.03 MB
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Checksum (MD5)
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Author(s)
Nordman, Jared T.
Kozhevnikova, Elena N.
Verrijzer, C. Peter
Pindyurin, Alexey V.
Andreyeva, Evgeniya N.
Shloma, Victor V.
Zhimulev, Igor F.
Orr-Weaver, Terry
Date Issued
October 2014
Journal
Cell Reports
Publisher
Elsevier
Citation
Nordman, Jared T., Elena N. Kozhevnikova, C. Peter Verrijzer, Alexey V. Pindyurin, Evgeniya N. Andreyeva, Victor V. Shloma, Igor F. Zhimulev, and Terry L. Orr-Weaver. “DNA Copy-Number Control through Inhibition of Replication Fork Progression.” Cell Reports 9, no. 3 (November 2014): 841–849.
Version
Final published version
Abstract
Proper control of DNA replication is essential to ensure faithful transmission of genetic material and prevent chromosomal aberrations that can drive cancer progression and developmental disorders. DNA replication is regulated primarily at the level of initiation and is under strict cell-cycle regulation. Importantly, DNA replication is highly influenced by developmental cues. In Drosophila, specific regions of the genome are repressed for DNA replication during differentiation by the SNF2 domain-containing protein SUUR through an unknown mechanism. We demonstrate that SUUR is recruited to active replication forks and mediates the repression of DNA replication by directly inhibiting replication fork progression instead of functioning as a replication fork barrier. Mass spectrometry identification of SUUR-associated proteins identified the replicative helicase member CDC45 as a SUUR-associated protein, supporting a role for SUUR directly at replication forks. Our results reveal that control of eukaryotic DNA copy number can occur through the inhibition of replication fork progression.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2014.10.005
