Open research questions in DNA Repair Mechanisms
136 unresolved questions extracted from the limitations and future-work sections of 361 DNA Repair Mechanisms papers in our library. Each links back to the study that raised it.
What the literature leaves open
The mechanism behind the decreases in insertion rates is unknown, - The mutation accumulation approach has drawbacks for inferring mechanism, - Alternative models need to be considered
Two distinct Okazaki fragment failure modes dominate mutagenesis in the absence of flap endonuclease 1 · 2026 · DOIInvestigating the mechanism behind the decrease in insertion rates in late replicating rad27Δ cells, - Exploring alternative models for point mutagenesis during genome replication and repair, - Assessing the role of Rad27 in other pathways and processes
Two distinct Okazaki fragment failure modes dominate mutagenesis in the absence of flap endonuclease 1 · 2026 · DOIInvestigate the role of other DNA repair pathways in transcriptional recovery, - Examine the effects of oxidative stress on transcription in different cell types
Elucidating how ATR selectively localizes to TGF-β-induced EMT gene promoters, - Investigating the extensive function of the LINC complex in modulating heterochromatin in response to mechanical cues
Emerging roles of ATR beyond DNA damage repair: orchestrating transcriptional reprogramming during epithelial-to-mesenchymal transition · 2026 · DOIThe gap in understanding ATR's role in EMT and its implications for cancer metastasis and therapy resistance. The need to investigate how ATR intersects with EMT transcriptional reprogramming. The lack of understanding of ATR's function in microenvironmental cues, such as ECM rigidity.
Emerging roles of ATR beyond DNA damage repair: orchestrating transcriptional reprogramming during epithelial-to-mesenchymal transition · 2026 · DOIThe complexity of the Fanconi anemia pathway and its role in genomic stability. The difficulty in targeting NHEJ in MLL-r leukemia. The need to develop effective therapeutic strategies for MLL-r leukemia.
The Fanconi anemia pathway restrains MLL-rearranged leukemogenesis through suppressing non-homologous end joining-mediated genomic instability · 2026 · DOIThe role of the Fanconi anemia pathway in MLL-rearranged leukemogenesis is not well understood. The mechanisms by which the FA pathway suppresses genomic instability in MLL-r leukemia are not clear. The therapeutic potential of targeting NHEJ in MLL-r leukemia has not been fully explored.
The Fanconi anemia pathway restrains MLL-rearranged leukemogenesis through suppressing non-homologous end joining-mediated genomic instability · 2026 · DOIThe paper identifies a gap in understanding the biology of HR deficient breast cancer. There is a need to better understand the mechanisms that support the fitness of HR deficient cells. The paper aims to increase the effectiveness of treatment for HR deficient breast cancer.
PUM3 is an essential suppressor of replication stress in homologous recombination deficient breast cancer · 2026 · DOIinvestigation of the genetic basis of temperature-dependent recombination remodelling, - analysis of the role of SNI1 in other accessions and hybrids, - study of the relationship between SNI1 and other genes involved in crossover regulation
The genetic basis of temperature-dependent recombination remodelling is not well understood. The role of SNI1 in regulating crossover formation is not clear. The relationship between temperature and crossover frequency is not fully elucidated.
Although this minisatellite harbors extraordinary allelic diversity in humans, the functional consequences of most naturally occurring variants remain unknown.
PRDM9-mediated meiotic hotspot specification is constrained in humans despite extensive sequence diversity · 2026 · DOIReplication stress is a major source of genome instability in cancer, yet the genomic features that determine where DNA double-strand breaks (DSBs) arise remain incompletely defined.
An integrated genome-wide resource reveals distinct replication environments of DNA breakage in human cancer cell lines · 2026 · DOIYet whether DSB end-processing enzymes themselves encode tunable phase separation that potentiates resection remains unclear.
Dna2-intrinsic condensation regulates DNA end resection and reveals evolutionary redistribution of condensate grammar · 2026 · DOIRadiation therapy (RT) resistance remains a major clinical challenge, yet biomarkers guiding precision radiosensitization are lacking.
Rac1 and CHK1 Converge on Abi-1 to Regulate DNA Repair Dependency and Treatment Response in Human Cancers · 2026 · DOIHow broken DNA ends loaded with RAD51 filaments are brought toward their repair template in the crowded 3D genome is currently poorly understood.
However, a comprehensive pan-cancer analysis revealing the role of the RPA gene family in cancer progression remains lacking.
Replication protein A in cancer: a pan-cancer analysis targeting on liver hepatocellular carcinoma · 2026 · DOIYet hotspot marking alone is insufficient: double-strand break formation requires assembly of the SPO11-TOPOVIBL catalytic machinery together with accessory proteins on the chromosome axis, linking recombination initiation to loop-axis organization.
While the genoprotective functions of FANCD2 have been extensively characterized, its specific biological roles and molecular regulatory mechanisms in the malignant progression of PM remain poorly understood.
FANCD2 knockdown suppresses malignant phenotypes and is associated with caspase/PARP-mediated apoptosis in NCI-H2052 pleural mesothelioma cells · 2026 · DOIAlthough the mechanisms underlying these processes are not yet fully understood, R-loops may play an important role in initiating gene amplification.
While PARP inhibitors (PARPi) have transformed the care of advanced HGSOC, PARPi resistance poses a major limitation to their clinical utility.
However, the mechanism of the facilitation of Mcm2 transferring parental histones to the lagging strand while moving along the leading strand remains unclear.
DNA polymerase delta governs parental histone transfer to DNA replication lagging strand · 2024 · DOIHow Rad26 distinguishes between RNA polymerase II (Pol II) stalled at a DNA lesion or other obstacles and what role Elf1 plays in this process remains unknown.
Elf1 promotes Rad26’s interaction with lesion-arrested Pol II for transcription-coupled repair · 2024 · DOIHowever, the mechanism governing alt-NHEJ pathway choice, particularly its association with DSB complexity, remains elusive due to the absence of a suitable reporter system.
Our understanding of the DNA damage responses of human cells to radiation has increased remarkably over the recent years although some notable signaling events remain to be discovered.
Alterations in hematopoietic stem cells (HSC) have been reported, but little is known regarding the bone marrow (BM) stroma.
Role of the mesenchymal stromal cells in bone marrow failure of Fanconi Anemia patients · 2024 · 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
- A CDK1 phospho-switch reprograms TRAIP to unload replisomes in mitosis · bioRxiv · 2026
- Genome instability triggers intercellular DNA transfer between human cells · Cell · 2026
- Mcm10 and RecQL4 Drive the Activation of the Eukaryotic Replicative DNA Helicase CMG · bioRxiv · 2026
- A non-catalytic role for RFC in PCNA-mediated processive DNA synthesis · Cell · 2026
- Evolutionary specialization of Rad51 and Dmc1 tune recombination outcomes · bioRxiv · 2026
- DNA repair drives cisplatin-induced neuronal death · Cell · 2026
- DDIAS is a single-stranded DNA-binding effector of the TOPBP1-CIP2A complex in mitosis · bioRxiv · 2026
- Structure of the Pre-Initiation Complex Explains CMGE Biogenesis · bioRxiv · 2026
- Regulation of Pfh1 helicase activity by nucleic acid interactions and mitochondrial SSB · Proceedings of the National Academy of Sciences · 2026
- Plant MutS Homolog 1 is a mismatch-directed nuclease required for organelle genome maintenance · bioRxiv (Cold Spring Harbor Laboratory) · 2026
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