New Discoveries on Protein Recruitment and Regulation during the Early Stages of the DNA Damage Response Pathways

Maintaining genomic stability and properly repairing damaged DNA is essential to staying healthy and preserving cellular homeostasis. The five major pathways involved in repairing eukaryotic DNA include base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), non-homologous end joining (NHEJ), and homologous recombination (HR). When these pathways do not properly repair damaged DNA, genomic stability is compromised and can contribute to diseases such as cancer. It is essential that the causes of DNA damage and the consequent repair pathways are fully understood, yet the initial recruitment and regulation of DNA damage response proteins remains unclear. In this review, the causes of DNA damage, the various mechanisms of DNA damage repair, and the current research regarding the early steps of each major pathway were investigated.

• Publication year

  2024

• Venue

  International Journal of Molecular Sciences

• Publication date

  2024-01-30

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3390/ijms25031676PMID 38338953PMCID 10855619
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1–BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy

  2023cited by this paper
• DNA-PK is activated by SIRT2 deacetylation to promote DNA double-strand break repair by non-homologous end joining

  2023cited by this paper
• A half century of exploring DNA excision repair in chromatin

  2023cited by this paper
• Structure and mechanism in non-homologous end joining.

  2023cited by this paper
• Unexpected moves: a conformational change in MutSα enables high-affinity DNA mismatch binding

  2023cited by this paper
• Phosphorylation of DNA-PKcs at the S2056 cluster ensures efficient and productive lymphocyte development in XLF-deficient mice

  2023cited by this paper
• ATM phosphorylates the FATC domain of DNA-PKcs at threonine 4102 to promote non-homologous end joining

  2023cited by this paper
• Structural characterization of transcription-coupled repair protein UVSSA and its interaction with TFIIH protein.

  2023cited by this paper
• Key role of phosphorylation sites in ATPase domain and Linker region of MLH1 for DNA binding and functionality of MutLα

  2023cited by this paper
• The Impact of Human DNA Glycosylases on the Activity of DNA Polymerase β toward Various Base Excision Repair Intermediates

  2023cited by this paper
• Cryo-EM visualization of DNA-PKcs structural intermediates in NHEJ

  2023influential reference
• The regulation of DNA end resection by chromatin response to DNA double strand breaks

  2022cited by this paper
• Cryogenic electron microscopy structures reveal how ATP and DNA binding in MutS coordinates sequential steps of DNA mismatch repair

  2022cited by this paper
• Global and transcription-coupled repair of 8-oxoG is initiated by nucleotide excision repair proteins

  2022cited by this paper
• Histone deacetylation regulates nucleotide excision repair through an interaction with the XPC protein

  2022cited by this paper
• Histone variants H3.3 and H2A.Z/H3.3 facilitate excision of uracil from nucleosome core particles.

  2022influential reference
• Insertions and deletions in protein evolution and engineering.

  2022cited by this paper
• Cryo-EM structure of the Mre11-Rad50-Nbs1 complex reveals the molecular mechanism of scaffolding functions.

  2022cited by this paper
• MutS functions as a clamp loader by positioning MutL on the DNA during mismatch repair

  2022cited by this paper
• Exploiting the distinctive properties of the bacterial and human MutS homolog sliding clamps on mismatched DNA

  2022cited by this paper
• BRCA1-dependent and independent recruitment of PALB2-BRCA2-RAD51 in the DNA damage response and cancer.

  2022cited by this paper
• Chaperones for dancing on chromatin: Role of post-translational modifications in dynamic damage detection hand-offs during nucleotide excision repair

  2021cited by this paper
• Autophosphorylation transforms DNA-PK from protecting to processing DNA ends.

  2021influential reference
• UV Radiation in DNA Damage and Repair Involving DNA-Photolyases and Cryptochromes

  2021cited by this paper
• Structure of the human ATM kinase and mechanism of Nbs1 binding

  2021cited by this paper
• Structural basis of human transcription–DNA repair coupling

  2021cited by this paper
• Guardians of the Genome: BRCA2 and Its Partners

  2021cited by this paper
• BARD1 reads H2A lysine 15 ubiquitination to direct homologous recombination

  2021cited by this paper
• DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy

  2021cited by this paper
• RNF168-mediated localization of BARD1 recruits the BRCA1-PALB2 complex to DNA damage

  2021cited by this paper
• Structural insight into BRCA1-BARD1 complex recruitment to damaged chromatin.

  2021cited by this paper
• Transcription-coupled nucleotide excision repair: New insights revealed by genomic approaches.

  2021cited by this paper
• USP44 Stabilizes DDB2 to Facilitate Nucleotide Excision Repair and Prevent Tumors

  2021cited by this paper
• The selection process of licensing a DNA mismatch for repair

  2021cited by this paper
• Structural basis for the coiled-coil architecture of human CtIP

  2021cited by this paper
• DNA Mismatch Repair and its Role in Huntington’s Disease

  2021influential reference
• Repair of DNA Double-Strand Breaks by the Nonhomologous End Joining Pathway.

  2021cited by this paper
• Mispair-bound human MutS–MutL complex triggers DNA incisions and activates mismatch repair

  2021cited by this paper
• Mismatch Repair Pathway, Genome Stability and Cancer

  2020cited by this paper
• New insights into abasic site repair and tolerance.

  2020cited by this paper
• The cooperative action of CSB, CSA, and UVSSA target TFIIH to DNA damage-stalled RNA polymerase II

  2020influential reference
• Ubiquitination of DNA Damage-Stalled RNAPII Promotes Transcription-Coupled Repair.

  2020cited by this paper
• DNA-PKcs: A Multi-Faceted Player in DNA Damage Response

  2020cited by this paper
• Focus on DNA Glycosylases—A Set of Tightly Regulated Enzymes with a High Potential as Anticancer Drug Targets

  2020cited by this paper
• A novel DDB2 mutation causes defective recognition of UV-induced DNA damages and prevalent equine squamous cell carcinoma.

  2020cited by this paper
• Chromatin recruitment of OGG1 requires cohesin and mediator and is essential for efficient 8-oxoG removal

  2020cited by this paper
• Recurrent mismatch binding by MutS mobile clamps on DNA localizes repair complexes nearby

  2020cited by this paper
• Dynamic human MutSα–MutLα complexes compact mismatched DNA

  2020cited by this paper
• BRCA1/BARD1 site-specific ubiquitylation of nucleosomal H2A is directed by BARD1

  2020cited by this paper
• HDAC3 Is Required for XPC Recruitment and Nucleotide Excision Repair of DNA Damage Induced by UV Irradiation

  2020cited by this paper
• CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair

  2019cited by this paper
• Mechanism and regulation of DNA damage recognition in nucleotide excision repair

  2019cited by this paper
• Novel RNA and DNA strand exchange activity of the PALB2 DNA binding domain and its critical role for DNA repair in cells

  2019cited by this paper
• Mitochondrial electron transport chain, ROS generation and uncoupling (Review)

  2019cited by this paper
• USP7-mediated deubiquitination differentially regulates CSB but not UVSSA upon UV radiation-induced DNA damage

  2019cited by this paper
• Acetylation of the histone H3 tail domain regulates base excision repair on higher-order chromatin structures

  2019cited by this paper
• SIRT6 is a DNA double-strand break sensor

  2019cited by this paper
• NBS1 promotes the endonuclease activity of the MRE11‐RAD50 complex by sensing CtIP phosphorylation

  2019cited by this paper
• Clustered DNA Damage Induced by 2-20 eV Electrons and Transient Anions: General Mechanism and Correlation to Cell Death.

  2019cited by this paper
• Histone H2A Variants Enhance the Initiation of Base Excision Repair in Nucleosomes.

  2019influential reference
• HDAC6 regulates DNA damage response via deacetylating MLH1

  2019cited by this paper
• Fidelity of DNA replication—a matter of proofreading

  2018cited by this paper
• The complete structure of the human TFIIH core complex

  2018influential reference
• Dynamics of sister chromatids through the cell cycle: Together and apart

  2018cited by this paper
• MutS homolog sliding clamps shield the DNA from binding proteins

  2018cited by this paper
• Coordinated protein and DNA conformational changes govern mismatch repair initiation by MutS

  2018cited by this paper
• Homologous recombination and the repair of DNA double-strand breaks

  2018influential reference
• The essential and multifunctional TFIIH complex

  2018influential reference
• Carcinogens and DNA damage

  2018cited by this paper
• Cryo-EM structure of human DNA-PK holoenzyme

  2017cited by this paper
• Base excision repair of oxidative DNA damage: from mechanism to disease.

  2017cited by this paper
• Mechanisms of DNA damage, repair, and mutagenesis

  2017influential reference
• Human OGG1 activity in nucleosomes is facilitated by transient unwrapping of DNA and is influenced by the local histone environment.

  2017influential reference
• Not breathing is not an option: How to deal with oxidative DNA damage.

  2017cited by this paper
• Differential Ability of Five DNA Glycosylases to Recognize and Repair Damage on Nucleosomal DNA.

  2017influential reference
• DNA mismatch repair and its many roles in eukaryotic cells.

  2017cited by this paper
• Repair of oxidatively induced DNA damage by DNA glycosylases: Mechanisms of action, substrate specificities and excision kinetics.

  2017cited by this paper
• Common TFIIH recruitment mechanism in global genome and transcription-coupled repair subpathways

  2017cited by this paper
• Lysines 3241 and 3260 of DNA-PKcs are important for genomic stability and radioresistance.

  2016cited by this paper
• JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks

  2016cited by this paper
• Phosphorylated CtIP Functions as a Co-factor of the MRE11-RAD50-NBS1 Endonuclease in DNA End Resection.

  2016cited by this paper
• UV-induced proteolysis of RNA polymerase II is mediated by VCP/p97 segregase and timely orchestration by Cockayne syndrome B protein

  2016cited by this paper
• Combinatory effect of BRCA1 and HERC2 expression on outcome in advanced non-small-cell lung cancer

  2016cited by this paper
• The Ku70/80 ring in Non-Homologous End-Joining: easy to slip on, hard to remove.

  2016cited by this paper
• A ubiquitylation site in Cockayne syndrome B required for repair of oxidative DNA damage, but not for transcription-coupled nucleotide excision repair

  2016cited by this paper
• Dynamic Behavior of Secondary Electrons in Liquid Water at the Earliest Stage upon Irradiation: Implications for DNA Damage Localization Mechanism.

  2016cited by this paper
• The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage

  2016cited by this paper
• Ionizing radiation-induced DNA injury and damage detection in patients with breast cancer

  2015cited by this paper
• ATP‐dependent DNA binding, unwinding, and resection by the Mre11/Rad50 complex

  2015cited by this paper
• Mechanisms of ATM Activation.

  2015cited by this paper
• Two decades beyond BRCA1/2: Homologous recombination, hereditary cancer risk and a target for ovarian cancer therapy.

  2015cited by this paper
• Histone H1 couples initiation and amplification of ubiquitin signalling after DNA damage

  2015cited by this paper
• In cellulo phosphorylation of XRCC4 Ser320 by DNA-PK induced by DNA damage

  2015cited by this paper
• ATM-Dependent Phosphorylation of All Three Members of the MRN Complex: From Sensor to Adaptor

  2015cited by this paper
• An oxidative DNA "damage" and repair mechanism localized in the VEGF promoter is important for hypoxia-induced VEGF mRNA expression.

  2015cited by this paper
• Functional regulation of the DNA damage-recognition factor DDB2 by ubiquitination and interaction with xeroderma pigmentosum group C protein

  2015influential reference
• CtIP tetramer assembly is required for DNA-end resection and repair

  2014cited by this paper
• Genomic Instability and Cancer.

  2014cited by this paper
• Effects of Ionizing Radiation on Biological Molecules—Mechanisms of Damage and Emerging Methods of Detection

  2014cited by this paper
• The Structural Location of DNA Lesions in Nucleosome Core Particles Determines Accessibility by Base Excision Repair Enzymes*

  2013cited by this paper

• CircRNA14781 promotes olaparib resistance of ovarian cancer cells by regulating miR-330-5p/NGFR pathway

  2026cites this paper
• Effects of two typical organophosphate flame retardants on DNA damage of GT1-7 cells and relevant molecular mechanism.

  2025cites this paper
• FRA1 (FOSL1) suppresses neoplastic transformation and modulates radiation responses via transcriptional control of mitogenic and stress-responsive networks

  2025cites this paper
• PARP Inhibitors in Metastatic Castration-resistant Prostate Cancer: Rationale, Mechanisms, and Clinical Applications.

  2025cites this paper
• Mechanistic Insights into TDCPP-Induced DNA Damage in GT1-7 Cells.

  2025cites this paper
• Circular RNA circ_0004470 accelerates the occurrence of lung cancer by promoting DNA damage and cell cycle arrest

  2025cites this paper
• Role of Phages in Past Molecular Biology and Potentially in Future Biomedicine

  2025cites this paper
• Engineered celastrol liposomes with glycyrrhizic acid augment synergistic antitumor efficacy in breast cancer

  2025cites this paper
• Insights into the behaviour of phosphorylated DNA breaks from molecular dynamic simulations

  2024cites this paper
• Introducing the Role of Genotoxicity in Neurodegenerative Diseases and Neuropsychiatric Disorders

  2024cites this paper
• [Metastatic castration-resistant prostate cancer and PARP inhibitors: From tumor genomics to new therapeutic combinations].

  2024cites this paper