ArticleScience advances2024
APOBEC3A induces DNA gaps through PRIMPOL and confers gap-associated therapeutic vulnerability.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed, 32 citations in OpenAlex.
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- TET2 loss triggers ssDNA gap accumulation and heightened PARP inhibitor sensitivity.Nature communications · 2026Article
- Suppression of transcription-replication conflicts by sequence-coordinated actions of TRDMT1 and MutLα.Nature communications · 2026Article
- SMARCAL1 is a candidate therapeutic target for ALT-positive tumors.Genes & development · 2026Article
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- Lentivirus enables the detection of strand-specific ssDNA gaps by the DNA fiber spreading assay.Communications biology · 2026Article
- Squamous-state excursions activate APOBEC3A in cancer.bioRxiv : the preprint server for biology · 2026Article
- USP1 inhibition promotes RAD18-dependent PCNA degradation and BRCA1 synthetic lethality.bioRxiv : the preprint server for biology · 2026Article
- LIPT1 loss confers replication stress and PARP inhibitor sensitivity through PrimPol-mediated ssDNA gaps.Science advances · 2026Article
- Replication protein A protects lagging strand gaps, restricting PARP inhibitor-induced synthetic lethality in BRCA1-deficient tumors.Nucleic acids research · 2026Article
- Understanding single stranded DNA gaps: from formation to fate.The Biochemical journal · 2026Review
- RPA exhaustion activates SLFN11 to eliminate cells with heightened replication stress.Nature cell biology · 2026Article
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- BRCA2 deficiency and replication stress drive APOBEC3-Mediated genomic instability.Nature communications · 2025Article
- APOBEC3A-Induced DNA Damage Drives Polymerase θ Dependency and Synthetic Lethality in Cancer.bioRxiv : the preprint server for biology · 2025Article
- Emerging drivers of DNA repeat expansions.Biochemical Society transactions · 2025Review
- Mechanisms and regulation of DNA end resection in the maintenance of genome stability.Nature reviews. Molecular cell biology · 2025Review
- Mechanism of DNA replication fork breakage and PARP1 hyperactivation during replication catastrophe.Science advances · 2025Article
- APOBEC3A deaminates CTG hairpin loops to promote fragility and instability of expanded CAG/CTG repeats.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- PARG inhibitor sensitivity correlates with accumulation of single-stranded DNA gaps in preclinical models of ovarian cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Mutation signatures associated with apolipoprotein B mRNA editing catalytic polypeptide-like 3A/B (APOBEC3A/B) cytidine deaminases are prevalent across cancers, implying their roles as mutagenic drivers during tumorigenesis and tumor evolution. APOBEC3A (A3A) expression induces DNA replication stress and increases the cellular dependency on the ataxia telangiectasia and Rad3-related (ATR) kinase for survival. Nonetheless, how A3A induces DNA replication stress remains unclear. We show that A3A induces replication stress without slowing replication forks. We find that A3A induces single-stranded DNA (ssDNA) gaps through PrimPol-mediated repriming. A3A-induced ssDNA gaps are repaired by multiple pathways involving ATR, RAD51, and translesion synthesis. Both ATR inhibition and trapping of poly(ADP-ribose) polymerase (PARP) on DNA by PARP inhibitor impair the repair of A3A-induced gaps, preferentially killing A3A-expressing cells. When used in combination, PARP and ATR inhibitors selectively kill A3A-expressing cells synergistically in a manner dependent on PrimPol-generated gaps. Thus, A3A-induced replication stress arises from PrimPol-generated ssDNA gaps, which confer a therapeutic vulnerability to gap-targeted DNA repair inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.