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Updated: Apr 1, 2026

Detection of Post-Replicative Gaps Accumulation and Repair in Human Cells Using the DNA Fiber Assay
Published on: February 3, 2022
Understanding single stranded DNA gaps: from formation to fate
Sonal Garg1, George-Lucian Moldovan1
1Department of Molecular and Precision Medicine, The Pennsylvania State University College of Medicine, Hershey, PA 17033, U.S.A.
Abstract:
Single-stranded DNA gaps (ssDNA gaps) have emerged as a potential indicator of therapeutic response in cancer. Accumulation of ssDNA gaps is associated with increased sensitivity of cancer cells to genotoxic therapies like PARP inhibitors (PARPi) and cisplatin chemotherapy. However, efficient repair or suppression of ssDNA gap formation is associated with therapy resistance and treatment failure. Therefore, understanding how ssDNA gaps form and are repaired can help identify biomarkers that can guide new treatment strategies to overcome resistance. In this review, we discuss different sources of ssDNA gap formation and the repair mechanisms that have been characterized to date. We bring together current knowledge on how these gaps are processed and what their ultimate fate may be. Finally, we discuss how established drugs like PARPi, hydroxyurea, and platinum compounds, induce and/or exploit ssDNA gaps. Throughout this review, we highlight ssDNA gaps as a potential therapeutic vulnerability that can be used to advance personalized cancer therapy.
Insights
Single-stranded DNA gaps (ssDNA gaps) indicate cancer therapy response. Understanding ssDNA gap formation and repair can reveal vulnerabilities to overcome treatment resistance and advance personalized cancer therapy.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Single-stranded DNA gaps (ssDNA gaps) are linked to cancer therapeutic responses.
- Increased ssDNA gaps correlate with sensitivity to genotoxic therapies like PARP inhibitors (PARPi) and cisplatin.
- Efficient ssDNA gap repair confers resistance to cancer treatments.
Purpose of the Study:
- To review the sources of ssDNA gap formation and their repair mechanisms.
- To synthesize current knowledge on ssDNA gap processing and outcomes.
- To highlight ssDNA gaps as a therapeutic vulnerability for personalized cancer therapy.
Main Methods:
- Literature review of ssDNA gap formation and repair pathways.
- Analysis of the role of ssDNA gaps in response to genotoxic agents.
- Discussion of therapeutic strategies targeting ssDNA gaps.
Main Results:
- ssDNA gaps arise from various sources and are processed by specific repair pathways.
- Drug resistance is associated with efficient ssDNA gap suppression.
- Established drugs like PARPi and platinum compounds induce or exploit ssDNA gaps.
Conclusions:
- ssDNA gaps represent a critical factor in cancer therapy response and resistance.
- Targeting ssDNA gap formation or repair offers a promising strategy for overcoming treatment failure.
- Further research into ssDNA gaps can guide the development of novel personalized cancer treatments.
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