DNA damage repair

Eukaryotic cells employ a plethora of processes to repair different types of DNA lesions, which together are crucial to the maintenance of genomic integrity. Failure to repair DNA damage underlies cancer development and genetic disorders such as Fanconi anaemia, and repair pathways are also involved in other physiological processes such as immunity and ageing. Research into DNA damage repair has gradually shifted from studying the functions of specific repair pathways to understanding how they are integrated into the DNA damage response. It is now becoming clear that different repair pathways can crosstalk, owing to the capacity of certain proteins to function in the signalling and repair of different DNA lesions. Furthermore, it has been demonstrated that DNA repair factors and pathways are intricately connected with cellular processes such as DNA replication, transcription and protein post-translational modifications.

In this specially commissioned Focus issue, we highlight the crosstalk between different DNA damage repair pathways, their relationships with other cellular processes and the implications for physiology and disease. Alan D'Andrea and colleagues discuss the repair of DNA interstrand crosslinks by the Fanconi anaemia pathway, which involves components of different repair processes, and which also functions in DNA replication and cell cycle regulation. Thomas Kunkel and colleagues describe ribonucleotide incorporation into DNA during replication and the ensuing DNA damage and its repair by different mechanisms. Niels Mailand and colleagues delve into the complex crosstalk between signalling by ubiquitin, SUMO and other ubiquitin-like modifiers in the repair of DNA double-strand breaks (DSBs). Last but not least, Eros Lazzerini-Denchi and Agnel Sfeir describe how the DNA damage response is kept in check at telomeres to avoid chromosomal rearrangements and tumorigenesis, and how telomere research has helped to uncover key steps in DSB repair. The Focus issue also features a Comment by Tomas Lindahl on the experimental properties and advantages of keeping DNA in the organic solvent glycol.