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Updated: Jun 12, 2026
07:27
Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
Published on: April 29, 2010
Break-induced replication requires all essential DNA replication factors except those specific for pre-RC assembly.
John R Lydeard1, Zachary Lipkin-Moore, Yi-Jun Sheu
1Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, USA.
Genes & Development
|June 3, 2010
Summary
Break-induced replication (BIR) uses DNA replication factors to repair double-strand breaks (DSBs). This process requires the replicative helicase and Cdc7 kinase but not origin recognition complex (ORC) or Cdc6.
Area of Science:
- Molecular Biology
- DNA Repair
- Cell Cycle Regulation
Background:
- Break-induced replication (BIR) is a homologous recombination (HR) pathway crucial for repairing DNA double-strand breaks (DSBs) when only one end has homology.
- BIR necessitates the involvement of all three major replicative DNA polymerases, including the Pol32 subunit.
Purpose of the Study:
- To elucidate the specific DNA replication factors and regulatory proteins involved in the BIR pathway.
- To investigate the roles of origin recognition complex (ORC), Cdc6, and Cdc7 kinase in BIR.
- To examine the influence of PCNA ubiquitination and sumoylation on BIR.
Main Methods:
- Genetic analysis using specific alleles and mutants.
- Assessing the requirement of various proteins and complexes for BIR.
- Investigating the function of PCNA variants in BIR.
Main Results:
- BIR requires the replicative DNA helicase (Cdc45, GINS, Mcm2-7) and Cdt1.
- Origin recognition complex (ORC) and Cdc6, essential for pre-replication complex (pre-RC) formation, are dispensable for BIR.
- Cdc7 kinase is essential for BIR, similar to its roles in DNA replication initiation and post-replication repair (PRR).
- PCNA ubiquitination and sumoylation have minor roles, while specific PCNA alleles inhibiting BIR are dominant inhibitors.
Conclusions:
- Origin-independent BIR relies on the interplay between canonical DNA replication machinery and post-replication repair (PRR) pathways.
- The findings highlight a distinct requirement for replication factors in BIR compared to origin-licensed replication.
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