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Updated: Jul 4, 2026
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Detection of Post-Replicative Gaps Accumulation and Repair in Human Cells Using the DNA Fiber Assay
Published on: February 3, 2022
PCNA modifications for regulation of post-replication repair pathways.
Kyoo-young Lee1, Kyungjae Myung
1Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive, Bethesda, MD 20892 USA.
Molecules and Cells
|June 6, 2008
Summary
Post-replication repair (PRR) pathways bypass DNA damage to prevent replication stalling. PCNA ubiquitination determines whether error-prone or error-free bypass mechanisms are used, crucial for preventing double-strand breaks and cancer.
Area of Science:
- Molecular Biology
- DNA Repair Mechanisms
- Cellular Stress Response
Background:
- Stalled DNA replication forks trigger post-replication repair (PRR) pathways to bypass DNA damage.
- Proliferating cell nuclear antigen (PCNA) is a key regulator that dictates which PRR pathway is utilized.
- Failure to repair stalled forks can lead to double-strand breaks (DSBs), genomic instability, and cancer.
Purpose of the Study:
- To elucidate the mechanisms by which PCNA ubiquitination regulates distinct PRR pathways.
- To understand the roles of translesion synthesis (TLS) polymerases and template switching in DNA damage bypass.
- To highlight the evolutionary conservation and tumor suppressor function of PRR.
Main Methods:
- Investigated PCNA ubiquitination at K164 catalyzed by Rad6/Rad18 complex in yeast.
- Analyzed the role of PCNA polyubiquitination by Ubc13/Mms2/Rad5 complex.
- Examined the function of PCNA interaction and ubiquitin binding motifs in TLS polymerases.
Main Results:
- PCNA monoubiquitination at K164 by Rad6/Rad18 recruits TLS polymerases for error-prone damage bypass.
- PCNA polyubiquitination by Ubc13/Mms2/Rad5 directs error-free damage avoidance via template switching.
- Homologues of yeast PRR proteins are conserved in mammals, indicating conserved function.
Conclusions:
- PCNA ubiquitination status is critical for selecting between error-prone TLS and error-free template switching.
- PRR pathways are essential for maintaining genomic integrity and act as a tumor suppressor mechanism.
- Dysfunctional PRR is linked to increased cancer risk, underscoring its importance in human health.
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