Series |

DNA damage

Cells are continuously faced with endogenous stress (for example, during replication) and exogenous stress (for example, during exposure to ultraviolet radiation) that can ultimately lead to DNA damage. To preserve genomic integrity, cells have an arsenal of repair proteins that detect different types of damage and initiate the appropriate repair pathway or, if irreparable, induce cell cycle arrest and/or apoptosis. These responses need to be tightly regulated to ensure that repair pathways are only activated by genuine DNA damage and not, for example, in response to telomeres. This control is achieved by multiple levels of regulation, including checkpoint signalling, non-coding RNAs and post-translational modifications such as ubiquitylation. This article series explores the pathways that detect and repair different types of DNA damage, highlighting new control mechanisms in the DNA damage response and the implications of disrupted repair pathways for disease.


  • Nature Reviews Molecular Cell Biology | Review Article

    Recent insights into the roles of poly(ADP-ribose) polymerase 1 (PARP1) in mediating various DNA repair pathways, stabilizing DNA replication and modulating chromatin structure are being exploited clinically for the treatment of DNA repair-deficient cancers.

    • Arnab Ray Chaudhuri
    •  &  André Nussenzweig
  • Nature Reviews Molecular Cell Biology | Review Article

    Covalent DNA–protein crosslinks (DPCs) are induced by various compounds, which include widely used anticancer drugs, and are highly cytotoxic. Recent studies have revealed the mechanisms and the regulation of DPC repair pathways and suggest that components of these pathways can serve as targets for anticancer therapies.

    • Julian Stingele
    • , Roberto Bellelli
    •  &  Simon J. Boulton
  • Nature Reviews Molecular Cell Biology | Review Article

    In mammalian cells, DNA double-strand breaks (DSBs) are repaired predominantly by the non-homologous end joining (NHEJ) pathway, which includes subpathways that can repair different DNA-end configurations. Furthermore, the repair of some DNA-end configurations can be shunted to the auxiliary pathways of alternative end joining (a-EJ) or single-strand annealing (SSA).

    • Howard H. Y. Chang
    • , Nicholas R. Pannunzio
    • , Noritaka Adachi
    •  &  Michael R. Lieber
  • Nature Reviews Molecular Cell Biology | Review Article

    Structure-specific endonucleases (SSEs) function in concert with other DNA-remodelling enzymes and cell cycle control machineries in processes such as DNA adduct repair, Holliday junction processing and the response to replication stress. As SSEs have specificity for DNA structures rather than sequence, tight regulation of their activity is important to ensure genome stability.

    • Pierre-Marie Dehé
    •  &  Pierre-Henri L. Gaillard
  • Nature Reviews Molecular Cell Biology | Review Article

    Encounters and conflicts between the transcription and replication machineries are common and represent a major intrinsic source of genome instability. Recent data shed new light on the biological relevance of transcription–replication conflicts and the factors and mechanisms involved in either preventing or resolving them.

    • Tatiana García-Muse
    •  &  Andrés Aguilera
  • Nature Reviews Molecular Cell Biology | Review Article

    Signalling by ubiquitin, SUMO and other ubiquitin-like modifiers (UBLs), and crosstalk between these modifications, underlies cellular responses to DNA double-strand breaks (DSBs). Important insights have been gained into the mechanisms by which ubiquitin and UBLs regulate protein interactions at DSB sites to enable accurate repair in mammalian cells, thereby protecting genome integrity.

    • Petra Schwertman
    • , Simon Bekker-Jensen
    •  &  Niels Mailand