Freedom to err: The expanding cellular functions of translesion DNA polymerases

Article Cell Biology

SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence

Ubaldo Gioia et al.

Summary: SARS-CoV-2 causes DNA damage and alters the DNA damage response, leading to inflammation and cellular senescence.

NATURE CELL BIOLOGY (2023)

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Article Biochemistry & Molecular Biology

Direct visualization of transcription-replication conflicts reveals post-replicative DNA:RNA hybrids

Henriette Stoy et al.

Summary: The authors developed an EM-based method to visualize R-loops directly, finding that DNA:RNA hybrids accumulate behind replication forks and affect fork slowing and reversal in transcription-replication conflicts. Previous studies on R-loops obstructing replication fork progression lacked direct visualization and non-ambiguous research tools. This study directly visualized estrogen-induced R-loops on the human genome using EM and measured their frequency and size at the single-molecule level. Combining EM and immuno-labeling in bacterial head-on TRCs, DNA:RNA hybrids were frequently observed behind replication forks, impacting fork behavior in conflict regions.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2023)

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Article Multidisciplinary Sciences

Polymerase theta inhibition activates the cGAS-STING pathway and cooperates with immune checkpoint blockade in models of BRCA-deficient cancer

Jeffrey Patterson-Fortin et al.

Summary: Recently developed POL theta inhibitors have shown synthetic lethality in BRCA-deficient tumor models. In this study, the authors examined the effects of POL theta inhibition in immunocompetent models of BRCA-deficient breast cancer and pancreatic cancer. They found that POL theta inhibition induced innate and adaptive immune responses, resulting in increased micronuclei, pathway activation, gene expression, T cell infiltration and activation, dendritic cell activation, and upregulation of PD-L1 expression. Depletion of T cells compromised the efficacy of POL theta inhibition, while combination with anti-PD-1 immunotherapy enhanced antitumor effects. These findings demonstrate the immune responses induced by POL theta inhibition and provide a rationale for combining it with immune checkpoint blockade for the treatment of HR-deficient cancers.

NATURE COMMUNICATIONS (2023)

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Article Multidisciplinary Sciences

Polymerase iota (Pol t) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability

Sabrina F. Mansilla et al.

Summary: Recent studies have shown that the choice of a DNA damage tolerance pathway involves competition between PrimPol-mediated repriming and fork reversal. Pol t plays a unique role in regulating this pathway choice, with Pol t deficiency leading to PrimPol-dependent repriming and accelerated DNA replication. However, this excessive participation of PrimPol in DNA elongation can trigger chromosome instability and replication stress signals in Pol t-depleted cells, revealing an unexpected role of Pol t in protecting genome stability.

SCIENCE ADVANCES (2023)

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Article Medicine, Research & Experimental

POLQ inhibition elicits an immune response in homologous recombination-deficient pancreatic adenocarcinoma via cGAS/STING signaling

Grace Oh et al.

Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with specific vulnerabilities to certain therapies. Inactivation of the HR pathway and overexpression of POLQ are associated with PDAC. Knockdown of POLQ enhances tumor immune infiltration and can be used as a synthetic lethal approach to inhibit tumor growth.

JOURNAL OF CLINICAL INVESTIGATION (2023)

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Review Biochemistry & Molecular Biology

Roles of trans-lesion synthesis (TLS) DNA polymerases in tumorigenesis and cancer therapy

Jay Anand et al.

Summary: DNA damage tolerance and mutagenesis are characteristics of neoplastic cells. TLS DNA polymerases enable cells to replicate damaged genomes and also cause mutations. The dysregulation of TLS plays a role in the development of skin cancer and possibly other human cancers.

NAR CANCER (2023)

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Review Oncology

Leveraging the replication stress response to optimize cancer therapy

Emily Cybulla et al.

Summary: This review describes the impact of DNA damage tolerance pathways on genome stability, their connection with tumorigenesis, and their effects on cancer therapy response. It discusses the accumulation of single-strand DNA gaps and its impact on chemotherapy response, as well as the potential of different DNA damage tolerance factors as cancer targets. The review also outlines how the consequences of DNA damage tolerance mechanisms could lead to the discovery of new biomarkers for refined cancer therapies.

NATURE REVIEWS CANCER (2023)

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Article Biochemistry & Molecular Biology

SCAI promotes error-free repair of DNA interstrand crosslinks via the Fanconi anemia pathway

Lisa Schubert et al.

Summary: This study reveals an essential role of SCAI in ensuring error-free ICL repair upon activation of the FA pathway. SCAI forms a complex with Pol zeta and localizes to ICLs during DNA replication. In the absence of SCAI, HR-mediated ICL repair is defective, resulting in deletions and radial chromosomes.

EMBO REPORTS (2022)

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Article Biochemistry & Molecular Biology

POLO prevents MRE11-NBS1-CtIP-dependent fork breakage in the absence of BRCA2/RAD51 by filling lagging-strand gaps

Anjali Mann et al.

Summary: POLO plays an important role in repairing DNA double-strand breaks in HR-defective tumors. It is found that POLO processes stalled Okazaki fragments, preventing the accumulation of ssDNA gaps on lagging strands in the absence of RAD51. Inhibition of POLO's DNA polymerase activity leads to unprotected fork gaps, which are cleaved by the MRE11-NBS1-CtIP endonuclease, causing asymmetric single-ended DSBs that impede the survival of BRCA2-defective cells.

MOLECULAR CELL (2022)

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Article Biochemistry & Molecular Biology

POLQ seals post-replicative ssDNA gaps to maintain genome stability in BRCA-deficient cancer cells

Ondrej Belan et al.

Summary: POLQ is a key factor in DSB repair and its inhibitors show synthetic lethality in HR and Shieldin-deficient cancer cells. This study reveals that POLQ-deficient cells accumulate ssDNA gaps upon BRCA1/2 loss or PARP inhibitor treatment. POLQ can also skip gaps through microhomology-mediated end-joining, resulting in genomic alterations resembling those found in POLQ overexpressing cancers.

MOLECULAR CELL (2022)

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Article Cell Biology

POL? processes ssDNA gaps and promotes replication fork progression in BRCA1-deficient cells

Anna Schrempf et al.

Summary: Polymerase theta (POLO) is an error-prone DNA polymerase that is synthetically lethal in cancer cells with BRCA1/2 mutations. The study shows that POLO processes single-stranded DNA gaps in the absence of BRCA1, promoting replication fork progression and survival of BRCA1 mutant cells. The research also uncovers suppressors of the POLO-BRCA1 interaction, including NBN and CDK6, which contribute to ssDNA gap formation and exacerbate replication stress in BRCA1-deficient cells.

CELL REPORTS (2022)

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Article Biochemistry & Molecular Biology

Computational Analysis of Short Linear Motifs in the Spike Protein of SARS-CoV-2 Variants Provides Possible Clues into the Immune Hijack and Evasion Mechanisms of Omicron Variant

Anjana Soorajkumar et al.

Summary: Short linear motifs (SLiMs) are important for mediating protein-protein interactions, and viruses utilize these motifs to disrupt the host system. Through sequence analysis, four overriding SLiMs were identified in the SARS-CoV-2 Omicron variant, which may interfere with immune functions, cellular pathways, and contribute to viral infection and transmission. These SLiMs serve as potential therapeutic targets.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Biochemistry & Molecular Biology

Division of labor within the DNA damage tolerance system reveals non-epistatic and clinically actionable targets for precision cancer medicine

Aldo Spanjaard et al.

Summary: PCNA-ubiquitination and REV1 play distinct roles in DNA damage tolerance, particularly in tolerating cisplatin lesions. Polymerase Kappa is essential in tolerating multiple genotoxic lesions, including cisplatin lesions.

NUCLEIC ACIDS RESEARCH (2022)

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Article Multidisciplinary Sciences

Host translesion polymerases are required for viral genome integrity

Sebastian Zeltzer et al.

Summary: Human cells have multiple specialized DNA polymerases for chromosomal DNA synthesis and repair, while complex DNA viruses may rely on host polymerases for synthesis. This study shows that error-prone Y-family polymerases can restrict human cytomegalovirus genome synthesis, while other TLS polymerases are required for optimal replication. Host polymerases also suppress viral genome rearrangements, indicating their role in ensuring viral genome stability.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

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Article Oncology

AXL and Error-Prone DNA Replication Confer Drug Resistance and Offer Strategies to Treat EGFR-Mutant Lung Cancer

Ashish Noronha et al.

Summary: EGFR inhibitors activate endogenous mutators in lung cancer cells, leading to drug resistance. Inhibiting this process can prevent drug resistance.

CANCER DISCOVERY (2022)

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Article Multidisciplinary Sciences

MAD2L2 promotes replication fork protection and recovery in a shieldin-independent and REV3L-dependent manner

Ines Paniagua et al.

Summary: MAD2L2, a member of the shieldin complex, protects stalled replication forks from excessive resection. Its loss leads to uncontrolled DNA resection, causing genomic damage. MAD2L2 functions independently of shieldin and cooperates with REV3L and REV1 to promote fork stability.

NATURE COMMUNICATIONS (2022)

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Review Pharmacology & Pharmacy

Translesion synthesis inhibitors as a new class of cancer chemotherapeutics

Seema M. Patel et al.

Summary: Translesion synthesis (TLS) is a DNA damage tolerance mechanism that plays a primary role in replicating past DNA lesions induced by genotoxic agents in cancer. Inhibitors targeting various TLS DNA polymerases or key protein-protein interactions in the TLS machinery have shown promise as a new class of anti-cancer adjuvant agents. Further studies are needed to determine the clinical potential and optimal targets for TLS inhibitors in combination therapies with current genotoxic chemotherapies.

EXPERT OPINION ON INVESTIGATIONAL DRUGS (2021)

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Article Biochemistry & Molecular Biology

CARM1 regulates replication fork speed and stress response by stimulating PARP1

Marie-Michelle Genois et al.

Summary: Recent research has shown that CARM1 interacts with PARP1 at DNA replication forks, slowing fork speed and promoting the stress response mechanism of fork reversal.

MOLECULAR CELL (2021)

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Article Cell Biology

Homology-directed repair protects the replicating genome from metabolic assaults

Kumar Somyajit et al.

Summary: The inhibition of ribonucleotide reductase leads to metabolic imbalance and accumulation of reactive oxygen species in cell nuclei, triggering a cascade of reactions involving ATM kinase and MRE11 nuclease. This process affects DNA replication and repair, impacting cancer evolution and tumor therapy.

DEVELOPMENTAL CELL (2021)

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Article Biochemistry & Molecular Biology

The Protexin complex counters resection on stalled forks to promote homologous recombination and crosslink repair

Richard O. Adeyemi et al.

Summary: Protexin complex, including the REV3 polymerase, establishes a novel fork protection pathway that counteracts fork resection, particularly at ICL stalled forks. This pathway acts independently of BRCA/RAD51-mediated fork stabilization and is crucial for maintaining genomic stability.

MOLECULAR CELL (2021)

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Article Biochemistry & Molecular Biology

Temporally distinct post-replicative repair mechanisms fill PRIMPOL-dependent ssDNA gaps in human cells

Stephanie Tirman et al.

Summary: By studying the mechanisms involved in maintaining genome stability, it was found that different pathways are responsible for filling single-stranded DNA gaps throughout the cell cycle, with different proteins and enzymes acting at different stages. Additionally, BRCA1 and BRCA2 play important roles in limiting MRE11 activity for gap filling, and simultaneously targeting fork reversal and gap filling enhances chemosensitivity in BRCA-deficient cells.

MOLECULAR CELL (2021)

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Article Biochemistry & Molecular Biology

Human DNA polymerase θ harbors DNA end-trimming activity critical for DNA repair

Karl E. Zahn et al.

Summary: The study reveals that DNA polymerase theta (pol theta) possesses a nuclease activity, distinct from its DNA synthesis activity, which plays a crucial role in the repair of DNA double-strand breaks. This nuclease activity requires metal ions, specific DNA nucleotides, and can trim or extend DNA based on the DNA repair context.

MOLECULAR CELL (2021)

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Review Biochemistry & Molecular Biology

To skip or not to skip: choosing repriming to tolerate DNA damage

Annabel Quinet et al.

Summary: Accurate DNA replication is constantly threatened by DNA lesions from various sources, and specialized DNA replication stress response pathways ensure replication fork progression in the presence of these lesions. These pathways include translesion DNA synthesis, template switching, and replication fork repriming, with the fine-tuned balance between them being crucial for genome integrity and cell fitness.

MOLECULAR CELL (2021)

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Article Multidisciplinary Sciences

Translesion polymerase eta both facilitates DNA replication and promotes increased human genetic variation at common fragile sites

Shyam Twayana et al.

Summary: The study reveals the crucial role of Pol eta in the replication of common fragile sites (CFSs), highlighting how its deficiency can lead to replication pausing and genetic variations. Presence of non-B DNA structures may increase replication hindrance. Activity of Pol eta in replicating through CFSs may result in genetic variations found in the human population at these sites.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Biochemistry & Molecular Biology

Human Rev1 relies on insert-2 to promote selective binding and accurate replication of stabilized G-quadruplex motifs

Amit Ketkar et al.

Summary: The study demonstrates that human Rev1 exhibits stronger affinity for parallel-stranded G4 structures, with amino acids in the alpha E helix of insert-2 identified as crucial for G4 binding. Mutations affecting G4 binding affinity were observed, with Pyridostatin exacerbating the increase in G4 mutation frequency. Wild-type and E466K hRev1 partially rescued mutagenic replication of G4 DNA, while E466A or Y470A mutants failed to suppress the PDS-induced increase in G4 mutation frequency.

NUCLEIC ACIDS RESEARCH (2021)

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Article Cell Biology

Disruption of DNA polymerase ζ engages an innate immune response

Sara K. Martin et al.

Summary: The disruption of pol zeta in mammalian cells leads to altered expression of 1,117 transcripts, showing signs of inducing an innate immune response. The increased expression of interferon-stimulated genes in these cells is driven by the cGAS-STING signaling pathway. Additionally, key interferon-stimulated chemokines are elevated in cells with disrupted Rev3l.

CELL REPORTS (2021)

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Article Oncology

REV1 Inhibition Enhances Radioresistance and Autophagy

Kanayo E. Ikeh et al.

Summary: Cancer therapy resistance, particularly to radiation treatment, remains a significant challenge. Inhibition of the TLS polymerase REV1 was previously shown to sensitize cancer cells to chemotherapy, but this study found a lack of radiosensitization and unexpected autophagy response with REV1 inhibition. REV1 may play a role in determining cancer treatment outcomes through modulation of autophagy and DNA damage responses.

CANCERS (2021)

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Article Biochemistry & Molecular Biology

The emerging determinants of replication fork stability

Tanay Thakar et al.

Summary: Replication fork reversal is a universal response to replication stress, but reversed forks are susceptible to nucleolytic digestion and rely on specific mechanisms for protection. The BRCA pathway plays a crucial role in maintaining fork stability, and its deficiency leads to degradation of reversed forks, genome instability, and chemosensitivity.

NUCLEIC ACIDS RESEARCH (2021)

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Review Cell Biology

REV7: Jack of many trades

Inge de Krijger et al.

Summary: REV7, also known as MAD2L2, is a versatile protein that interacts with various proteins to form different complexes, impacting a wide range of cellular processes. It plays important roles in translesion synthesis and mitotic progression, as well as being a central component in the shieldin complex involved in DNA double strand break repair.

TRENDS IN CELL BIOLOGY (2021)

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Review Cell Biology

Dealing with DNA lesions: When one cell cycle is not enough

Aleksandra Lezaja et al.

Summary: Genomic lesions are both essential for cellular adaptation and organismal evolution, but also pose a harmful risk for cancer and age-related diseases. Actively dividing cells frequently encounter endogenous genomic lesions in repetitive, heterochromatic, and late replicating regions, which are not immediately resolved but instead handled in subsequent cell cycle phases and even after mitotic cell division, which impacts genome organization, stability, and function.

CURRENT OPINION IN CELL BIOLOGY (2021)

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Article Biochemistry & Molecular Biology

DNA polymerase zeta contributes to heterochromatin replication to prevent genome instability

Barbara Ben Yamin et al.

Summary: The study highlights the crucial role of DNA polymerase zeta in bypassing DNA damage and cell proliferation, as well as the significance of REV3L's interactions with heterochromatin components in maintaining chromosome stability.

EMBO JOURNAL (2021)

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Article Biochemistry & Molecular Biology

PrimPol-mediated repriming facilitates replication traverse of DNA interstrand crosslinks

Daniel Gonzalez-Acosta et al.

Summary: DNA interstrand crosslinks (ICLs) induced by endogenous aldehydes or chemotherapeutic agents interfere with essential processes such as replication and transcription. Recognition and repair require the formation of an X-shaped DNA structure that may arise from convergence of two replication forks at the crosslink or traversing of the lesion by a single replication fork. PrimPol is essential for ICL traverse downstream of the lesion, and targeting PrimPol activity may enhance the efficacy of chemotherapy based on DNA crosslinking agents.

EMBO JOURNAL (2021)

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Article Cell Biology

Implications of inhibition of Rev1 interaction with Y family DNA polymerases for cisplatin chemotherapy

Jung-Hoon Yoon et al.

Summary: Chemotherapy with cisplatin is limited by its toxicity and risk of secondary malignancies. Targeting translesion synthesis (TLS) mechanisms in cancer cells, as opposed to normal cells, can exacerbate the toxicity and tumorigenicity of cisplatin-based chemotherapeutics.

GENES & DEVELOPMENT (2021)

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Article Biochemistry & Molecular Biology

DNA polymerase λ promotes error-free replication through Watson-Crick impairing N1-methyl-deoxyadenosine adduct in conjunction with DNA polymerase ζ

Jung-Hoon Yoon et al.

Summary: The study demonstrates the essential role of Pol lambda in inserting the correct nucleotide T opposite 1-MeA, while Pol zeta is responsible for extending synthesis. The ability of Pol lambda to accommodate 1-MeA in a syn confirmation and form Hoogsteen base pair with T during DNA synthesis is highlighted. This adds a novel aspect to Pol lambda's function in translesion synthesis, in addition to its role as a scaffolding component for Pol zeta.

JOURNAL OF BIOLOGICAL CHEMISTRY (2021)

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Article Chemistry, Multidisciplinary

DNA Polymerase η Promotes the Transcriptional Bypass of N2-Alkyl-2′-deoxyguanosine Adducts in Human Cells

Ying Tan et al.

Summary: This study investigated the transcriptional bypass of DNA lesions by TLS polymerases, specifically focusing on N-2-alkyl-dG lesions in HEK293T cells. The results showed that N-2-alkyl-dG lesions strongly blocked transcription and led to specific mutations, with Pol eta playing a crucial role in transcriptional bypass efficiency. Additionally, the repair of N-2-nBu-dG lesions was found to be less affected by genetic depletion of Pol eta or Rev1, highlighting the diverse functions of TLS DNA polymerases.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

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Article Biochemistry & Molecular Biology

REV1-Polζ maintains the viability of homologous recombination-deficient cancer cells through mutagenic repair of PRIMPOL-dependent ssDNA gaps

Angelo Taglialatela et al.

Summary: BRCA1/2 mutant tumor cells accumulate ssDNA gaps and spontaneous mutations during DNA replication due to repriming by PRIMPOL. This accumulation is exacerbated by depletion of RAD18 or inhibition of REV1-Pol zeta, with JH-RE-06 treatment resulting in reduced mutation rates and loss of viability in BRCA1/2-deficient cells. REV1-Pol zeta inhibitors show preferential toxicity toward HR-deficient cancer cells and may be a potential treatment strategy for BRCA1/2 mutant tumors.

MOLECULAR CELL (2021)

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Article Cell Biology

ELOF1 is a transcription-coupled DNA repair factor that directs RNA polymerase II ubiquitylation

Yana van der Weegen et al.

Summary: ELOF1 serves as a missing link that facilitates RNAPII ubiquitylation, driving transcription-coupled repair and preventing replication stress. It acts as a specificity factor that binds and positions CRL4(CSA) for optimal RNAPII ubiquitylation, offering key insights into the molecular mechanisms of TCR.

NATURE CELL BIOLOGY (2021)

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Article Multidisciplinary Sciences

Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance

Diana Zatreanu et al.

Summary: The study identifies small molecule inhibitors targeting Pol theta polymerase activity that induce BRCA1/2 synthetic lethality, enhance PARP inhibitor effects, and address PARP inhibitor resistance caused by defects in the 53BP1/Shieldin pathway.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

Polθ reverse transcribes RNA and promotes RNA-templated DNA repair

Gurushankar Chandramouly et al.

Summary: The study reveals that human Pol theta can reverse transcribe RNA, incorporate deoxyribonucleotides on RNA with higher velocity and fidelity, and promote RNA-templated DNA repair synthesis in mammalian cells, suggesting that Pol theta was selected to accommodate template ribonucleotides during DNA repair.

SCIENCE ADVANCES (2021)

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Article Multidisciplinary Sciences

BRCA2 associates with MCM10 to suppress PRIMPOL-mediated repriming and single-stranded gap formation after DNA damage

Zhihua Kang et al.

Summary: BRCA2 is recruited to the replication fork through interaction with MCM10 to inhibit repriming and single-strand DNA gap formation after DNA damage. BRCA2-deficient cells exhibit radio-resistant DNA synthesis phenotype following DNA damage.

NATURE COMMUNICATIONS (2021)

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Article Oncology

A first-in-class polymerase theta inhibitor selectively targets homologous-recombination-deficient tumors

Jia Zhou et al.

Summary: The antibiotic novobiocin has been identified as a specific POLQ inhibitor with preclinical activity in homologous-recombination-deficient breast and ovarian tumors, including those with acquired PARP inhibitor resistance. This study suggests that novobiocin may be useful alone or in combination with PARP inhibitors for treating HR-deficient tumors.

NATURE CANCER (2021)

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Review Oncology

Targeting the DNA Repair Enzyme Polymerase theta in Cancer Therapy

Anna Schrempf et al.

Summary: Targeted cancer therapies focusing on POLQ, an error-prone translesion polymerase involved in DNA repair, represent a promising approach in personalized cancer treatment. Inhibition of POLQ, currently under development, shows potential for more effective cancer therapies in the future.

TRENDS IN CANCER (2021)

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Article Biochemistry & Molecular Biology

PRIMPOL-Mediated Adaptive Response Suppresses Replication Fork Reversal in BRCA-Deficient Cells

Annabel Quinet et al.

MOLECULAR CELL (2020)

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Review Oncology

The roles of RNA in DNA double-strand break repair

Aldo S. Bader et al.

BRITISH JOURNAL OF CANCER (2020)

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Article Biochemistry & Molecular Biology

HLTF Promotes Fork Reversal, Limiting Replication Stress Resistance and Preventing Multiple Mechanisms of Unrestrained DNA Synthesis

Gongshi Bai et al.

MOLECULAR CELL (2020)

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Article Multidisciplinary Sciences

Inhibition of the translesion synthesis polymerase REV1 exploits replication gaps as a cancer vulnerability

Sumeet Nayak et al.

SCIENCE ADVANCES (2020)

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Review Cell Biology

The plasticity of DNA replication forks in response to clinically relevant genotoxic stress

Matteo Berti et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2020)

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Article Biochemistry & Molecular Biology

Genetic Characterization of Three Distinct Mechanisms Supporting RNA-Driven DNA Repair and Modification Reveals Major Role of DNA Polymerase ζ

Chance Meers et al.

MOLECULAR CELL (2020)

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Article Multidisciplinary Sciences

REV1 inhibitor JH-RE-06 enhances tumor cell response to chemotherapy by triggering senescence hallmarks

Nimrat Chatterjee et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Article Biochemistry & Molecular Biology

Human DNA polymerase has reverse transcriptase activity in cellular environments

Yan Su et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2019)

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Article Biochemistry & Molecular Biology

Rad5 Recruits Error-Prone DNA Polymerases for Mutagenic Repair of ssDNA Gaps on Undamaged Templates

David Gallo et al.

MOLECULAR CELL (2019)

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Review Multidisciplinary Sciences

cGAS in action: Expanding roles in immunity and inflammation

Andrea Ablasser et al.

SCIENCE (2019)

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Article Biochemistry & Molecular Biology

A Small Molecule Targeting Mutagenic Translesion Synthesis Improves Chemotherapy

Jessica L. Wojtaszek et al.

CELL (2019)

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Review Cell Biology

DNA double-strand break repair-pathway choice in somatic mammalian cells

Ralph Scully et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2019)

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Article Multidisciplinary Sciences

Adaptive mutability of colorectal cancers in response to targeted therapies

Mariangela Russo et al.

SCIENCE (2019)

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Article Biochemistry & Molecular Biology

R-loop formation during S phase is restricted by PrimPol-mediated repriming

Sasa Svikovic et al.

EMBO JOURNAL (2019)

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Review Genetics & Heredity

Mechanisms of DNA Damage Tolerance: Post-Translational Regulation of PCNA

Wendy Leung et al.

GENES (2019)

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Article Genetics & Heredity

Genetic Control of Genomic Alterations Induced in Yeast by Interstitial Telomeric Sequencess

Anthony Moore et al.

GENETICS (2018)

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Article Biochemistry & Molecular Biology

Activity and fidelity of human DNA polymerase depend on primer structure

Andrey G. Baranovskiy et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2018)

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Article Genetics & Heredity

Genetic Control of Genomic Alterations Induced in Yeast by Interstitial Telomeric Sequencess

Anthony Moore et al.

GENETICS (2018)

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Review Biochemistry & Molecular Biology

Translesion and Repair DNA Polymerases: Diverse Structure and Mechanism

Wei Yang et al.

ANNUAL REVIEW OF BIOCHEMISTRY, VOL 87 (2018)

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Article Biochemistry & Molecular Biology

Dual Roles of Poly(dA:dT) Tracts in Replication Initiation and Fork Collapse

Anthony Tubbs et al.

CELL (2018)

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Article Multidisciplinary Sciences

SAMHD1 acts at stalled replication forks to prevent interferon induction

Flavie Coquel et al.

NATURE (2018)

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Article Oncology

DNA Polymerase Eta Prevents Tumor Cell-Cycle Arrest and Cell Death during Recovery from Replication Stress

Ryan P. Barnes et al.

CANCER RESEARCH (2018)

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Article Biochemistry & Molecular Biology

USP1 Is Required for Replication Fork Protection in BRCA1-Deficient Tumors

Kah Suan Lim et al.

MOLECULAR CELL (2018)

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Article Biology

Translesion polymerase kappa-dependent DNA synthesis underlies replication fork recovery

Peter Tonzi et al.

ELIFE (2018)

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Article Virology

The Translesion Polymerase Pol η Is Required for Efficient Epstein-Barr Virus Infectivity and Is Regulated by the Viral Deubiquitinating Enzyme BPLF1

Ossie F. Dyson et al.

JOURNAL OF VIROLOGY (2017)

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Article Biochemistry & Molecular Biology

Replication Fork Slowing and Reversal upon DNA Damage Require PCNA Polyubiquitination and ZRANB3 DNA Translocase Activity

Marko Vujanovic et al.

MOLECULAR CELL (2017)

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Article Multidisciplinary Sciences

Translesion synthesis DNA polymerase. exhibits a specific RNA extension activity and a transcription-associated function

Vamsi K. Gali et al.

SCIENTIFIC REPORTS (2017)

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Article Genetics & Heredity

DNA polymerases eta and kappa exchange with the polymerase delta holoenzyme to complete common fragile site synthesis

Ryan P. Barnes et al.

DNA REPAIR (2017)

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Article Biochemistry & Molecular Biology

Identification of Small Molecule Translesion Synthesis Inhibitors That Target the Rev1-CT/RIR Protein-Protein Interaction

Vibhavari Sail et al.

ACS CHEMICAL BIOLOGY (2017)

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Article Biochemistry & Molecular Biology

Human Translesion Polymerase κ Exhibits Enhanced Activity and Reduced Fidelity Two Nucleotides from G-Quadruplex DNA

Sarah Eddy et al.

BIOCHEMISTRY (2016)

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Article Biochemistry & Molecular Biology

PrimPol Is Required for Replicative Tolerance of G Quadruplexes in Vertebrate Cells

Davide Schiavone et al.

MOLECULAR CELL (2016)

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Article Oncology

Co-inhibition of pol θ and HR genes efficiently synergize with cisplatin to suppress cisplatin-resistant lung cancer cells survival

Chun-Hua Dai et al.

ONCOTARGET (2016)

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Article Cell Biology

Proteomic Profiling Reveals a Specific Role for Translesion DNA Polymerase η in the Alternative Lengthening of Telomeres

Laura Garcia-Exposito et al.

CELL REPORTS (2016)

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Article Genetics & Heredity

Genomic Scars Generated by Polymerase Theta Reveal the Versatile Mechanism of Alternative End-Joining

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