DNA copy-number control through inhibition of replication fork progression

Jared T. Nordman, Elena N. Kozhevnikova, C. Peter Verrijzer, Alexey V. Pindyurin, Evgeniya N. Andreyeva, Victor V. Shloma, Igor F. Zhimulev, Terry L. Orr-Weaver

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)841-849
Number of pages9
JournalCell Reports
Volume9
Issue number3
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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