Open research questions in DNA Repair Mechanisms
523 gap statements mined from DNA Repair Mechanisms papers in our 7.9M-paper local library, which holds 1,851 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.
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What the literature leaves open
Limited understanding of the mechanisms of action of splicing targeting drugs in NSCLC.
SPHINX31 acts as a SRPK1 inhibitor targeting the ATR / DNA ‐ PKcs / CHK1 replicative checkpoint to inhibit cell growth in non‐small cell lung cancer · 2026 · DOIThe impact of caffeine on cell cycle progression and DNA damage checkpoint signalling is not well understood. The molecular mechanisms of caffeine's effects on fission yeast are not fully elucidated. The potential applications of caffeine's radiomimetic-like effects in disease prevention and treatment are not well explored.
Revisiting the Radiomimetic-like Effects of Caffeine on Fission Yeast DNA: A Riddle in Need of Further Resolution · 2026 · DOIThe mechanisms by which nuclear mechanics regulate DNA repair remain unclear. The interplay between nuclear mechanics, microtubule-dependent forces and DSB mobility remains unclear.
The need for novel therapeutic strategies to inactivate MGMT and increase the efficacy of alkylating agents. The lack of understanding of the role of redox perturbing agents and nitric oxide-donors in MGMT inactivation.
Novel Pathways of Oxidative and Nitrosative Inactivation of the Human MGMT Protein in Colon Cancer and Glioblastoma Cells: Increased Efficacy of Alkylating Agents In Vitro and In Vivo · 2025 · DOIFurther studies are needed to elucidate WRN's precise physiological roles with cells and tissues. Investigation into the function of WRN in different DNA structural contexts is necessary. Research on the interaction between WRN and other proteins involved in DNA replication and repair is required.
Response to Replication Stress and Maintenance of Genome Stability by WRN, the Werner Syndrome Protein · 2024 · DOIThe precise role of WRN is unclear. There is a need to understand the physiological functions of WRN. The paper aims to address this gap by reviewing the current knowledge on WRN.
Response to Replication Stress and Maintenance of Genome Stability by WRN, the Werner Syndrome Protein · 2024 · DOIHowever, how the oocyte meiotic prophase checkpoint is regulated remains unclear.
The SOS response to DNA damage is particularly heterogeneous, but the origin of its spontaneous activation and its relationship to cell fate remain unclear.
Cyclic di-adenosine monophosphate couples DNA damage sensing to genome maintenance in mycobacteria, but how it regulates homologous recombination machinery beyond RecA remains unclear.
Direct engagement of mycobacterial RadA by c-di-AMP at a non-catalytic site suppresses its DNA-stimulated ATPase activity · 2026 · DOIMimosine, a non-proteinogenic amino acid derived from Leucaena species, is known to cause cell-cycle arrest and DNA strand breaks, yet its interaction with DNA repair pathways remains poorly understood.
Investigating the role of mimosine-induced genotoxic stress through DNA repair profiling · 2026 · DOIHowever, the detailed mechanisms by which PTMs modulate RAP80 activity remain to be fully elucidated.
However, the mechanisms, protein partners, and functions by which cohesin is involved in DNA repair remain unclear.
SMARCA5 facilitates cohesin localization at R-loops to prevent transcription-replication collisions · 2026 · DOIUnlike Polζ, which possesses robust DNA polymerase activity, biochemical assays suggest that Rev1 predominantly incorporates a "C" opposite any templating residues, but the biological relevance of this activity of Rev1 remains elusive.
Enzymatic and Structural Roles of Candida albicans Rev1 in DNA Damage Response and Disseminated Candidiasis · 2025 · DOIHowever, the relationship between JAML expression and radiosensitivity of CRC remains unclear.
Overexpression of JAML in colorectal cancer cells predicts higher radiosensitivity by inactivating ATR pathway · 2025 · DOIEsophageal cancer lacks characteristic mutations in DNA repair genes; therefore, DNA damage response (DDR) factors have not been widely explored as predictive biomarkers in esophageal cancer.
Esophageal Cancer Cells Exhibit Heterogeneity in DNA Double-Strand Break Repair and G2/M Checkpoint Arrest Associated With Cell Viability After Ionizing Radiation · 2025 · DOIHowever, Alt-EJ is often inhibited by classical nonhomologous end-joining (C-NHEJ) or homologous recombination, the precise impact of Alt-EJ on plant genome instability remains unclear.
Manipulating alternative end-joining alters carbon-ion beam-induced genome mutation profiles in Arabidopsis thaliana · 2025 · DOIThe plant TDP1 subfamily contains the canonical TDP1α gene and the TDP1β gene whose functions are not fully elucidated.
Exposure of Arabidopsis thaliana Mutants to Genotoxic Stress Provides New Insights for the Involvement of TDP1α and TDP1β genes in DNA‐Damage Response · 2024 · DOIAt present, the properties and functions of RPL13 have not been characterised in insects.
Bombyx mori RPL13 participates in UV ‐induced DNA damage repair of B. mori nucleopolyhedrovirus through interaction with Bm65 · 2024 · DOIHowever, the exact role of RUNX3 in cancer pathogenesis remains to be completely elucidated.
The biological implication of higher or lower repair capacity remains unclear; the inclusion of DNA repair as a biomarker in molecular epidemiological trials should elucidate the link between health and disease status.
Yet, how targeting downstream enzymes with small molecule inhibitors could affect this coordination remains unknown.
Impact of DNA ligase inhibition on the nick sealing of polβ nucleotide insertion products at the downstream steps of base excision repair pathway · 2024 · DOIWhile the impact of p53 deficiency on increasing DNA replication stress is known, the specific molecular mechanism underlying this phenomenon remains poorly understood.
R-loop formation contributes to mTORC1 activation-dependent DNA replication stress induced by p53 deficiency · 2024 · DOIThe role of NBS1 in DNA damage response is not fully understood. The mechanisms of ATR in radiation and etoposide induced DNA damage in the absence of NBS1 proteins are not fully understood.
Generation of NBS1 knockout in Chinese hamster cells revealed ATR role for radiation and etoposide induced DNA damage in absence of NBS1 proteins · 2026 · DOIATR is a DNA damage response kinase essential for male meiosis, but its role in female meiosis is poorly characterized.
The mechanism underlying selective ATR dependence in NBS1-deficient cells during G2 phase versus S-phase requires further mechanistic elucidation beyond the current Rad51 and chromosomal aberration…
Generation of NBS1 knockout in Chinese hamster cells revealed ATR role for radiation and etoposide induced DNA damage in absence of NBS1 proteins · 2026 · DOI
Most-cited papers in DNA Repair Mechanisms
- Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy · Nature · 2005 · 5,757 citations
- The DNA-damage response in human biology and disease · Nature · 2009 · 5,312 citations
- Instability and decay of the primary structure of DNA · Nature · 1993 · 4,636 citations
- Genome maintenance mechanisms for preventing cancer · Nature · 2001 · 3,082 citations
- DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation · Nature · 2003 · 2,768 citations
- ATM and ATR Substrate Analysis Reveals Extensive Protein Networks Responsive to DNA Damage · Science · 2007 · 2,603 citations
- The DNA damage response: putting checkpoints in perspective · Nature · 2000 · 2,505 citations
- Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes · Science · 2003 · 2,336 citations
- DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis · Nature · 2005 · 2,250 citations
- Checkpoints: Controls That Ensure the Order of Cell Cycle Events · Science · 1989 · 2,201 citations
Most recent work
- Replicative gaps in DNA damage tolerance, genome instability, and cancer therapy · Molecular Cell · 2026
- A CDK1 phospho-switch reprograms TRAIP to unload replisomes in mitosis · bioRxiv · 2026
- Micronuclei: origins, assays, mechanisms, diseases and treatments · Signal Transduction and Targeted Therapy · 2026
- Structure and function of the synaptonemal complex · The Journal of Cell Biology · 2026
- Molecular landscape and clinical translation of DNA damage response alterations in solid tumors: A pan-cancer perspective on precision oncology · Neoplasia · 2026
- Genome instability triggers intercellular DNA transfer between human cells · Cell · 2026
- Nucleotide salvage, genome instability, and potential therapeutic applications · Nucleic Acids Research · 2026
- Epigenetic consequences of DNA damage · Molecular Cell · 2026
- Structural insight into how RAD51 paralog exchange regulates RAD51 filament formation · Nature Structural & Molecular Biology · 2026
- The expanding roles of homologous recombination proteins in genome stability · The EMBO Journal · 2026
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