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The Relevance of G-Quadruplexes for DNA Repair

Journal

Publisher

MDPI
DOI: 10.3390/ijms222212599

Keywords

G-quadruplex; genome instability; homologous recombination; non-homologous end joining; nucleotide excision repair; translesion synthesis

Funding

  1. ERC Stg Grant [638988-G4DSB]
  2. Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [369799452-TRR237]
  3. Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy [EXC2151-390873048]
  4. Bonn-Melbourne Graduate School [GRK2168]

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In summary, G-quadruplex DNA structures play important roles in cellular function, but can also induce genome instability leading to tumorigenesis and genetic disorders. By interacting with DNA repair proteins and ligands, G4 structures can block specific DNA repair pathways.
DNA molecules can adopt a variety of alternative structures. Among these structures are G-quadruplex DNA structures (G4s), which support cellular function by affecting transcription, translation, and telomere maintenance. These structures can also induce genome instability by stalling replication, increasing DNA damage, and recombination events. G-quadruplex-driven genome instability is connected to tumorigenesis and other genetic disorders. In recent years, the connection between genome stability, DNA repair and G4 formation was further underlined by the identification of multiple DNA repair proteins and ligands which bind and stabilize said G4 structures to block specific DNA repair pathways. The relevance of G4s for different DNA repair pathways is complex and depends on the repair pathway itself. G4 structures can induce DNA damage and block efficient DNA repair, but they can also support the activity and function of certain repair pathways. In this review, we highlight the roles and consequences of G4 DNA structures for DNA repair initiation, processing, and the efficiency of various DNA repair pathways.

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