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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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A mitotic bookmark coordinates transcription and replication.

Chun-Yi Cho1, Patrick H O'Farrell1

  • 1Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.

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Summary
This summary is machine-generated.

To prevent collisions between DNA replication and transcription, Brd4 bookmarks mitotic chromosomes. Upon anaphase entry, Cdc7 is recruited to initiate replication and remove bookmarks, ensuring transcription starts later.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Collisions between DNA replication forks and transcription pose a threat to genome stability.
  • In early Drosophila embryos, replication starts immediately after mitosis, while transcription begins 3 minutes later.

Purpose of the Study:

  • Investigate the role of Brd4 and Cdc7 in coordinating replication and transcription during early Drosophila embryogenesis.
  • Determine how temporal ordering of replication and transcription initiation minimizes collisions.

Main Methods:

  • Utilized Drosophila melanogaster as a model organism.
  • Investigated the persistence of Brd4 on mitotic chromosomes.
  • Examined the recruitment of Cdc7 by Brd4.
  • Assessed the impact of Cdc7 inhibition on replication timing and transcription.

Main Results:

  • Brd4 persists on mitotic chromosomes as transcriptional bookmarks.
  • Brd4 recruits Cdc7 upon anaphase entry to specify early-replicating regions.
  • Cdc7 activity removes Brd4 bookmarks, deferring post-mitotic transcription.
  • Cdc7 inhibition delays replication, stabilizes Brd4 bookmarks, and causes premature transcription with elongation defects.

Conclusions:

  • Cdc7 triggers a functional switch in Brd4, enforcing temporal order of replication and transcription initiation.
  • This temporal ordering minimizes collisions between replication forks and transcripts.
  • The mechanism may explain the correlation between transcriptional activity and early replication.