Environmental DNA damaging agents continuously challenge the integrity of the genome by introducing a variety of DNA lesions. The DNA damage caused by environmental factors will lead to mutagenesis and subsequent carcinogenesis if they are not removed efficiently by repair pathways. Methods for detection of DNA damage and repair can be applied to identify, visualize, and quantify the DNA damage formation and repair events, and they enable us to illustrate the molecular mechanisms of DNA damage formation, DNA repair pathways, mutagenesis, and carcinogenesis. Ever since the discovery of the double helical structure of DNA in 1953, a great number of methods have been developed to detect various types of DNA damage and repair. Rapid advances in sequencing technologies have facilitated the emergence of a variety of novel methods for detecting environmentally induced DNA damage and repair at the genome‐wide scale during the last decade. In this review, we provide a historical overview of the development of various damage detection methods. We also highlight the current methodologies to detect DNA damage and repair, especially some next generation sequencing‐based methods.

The unique nucleolar environment, the repetitive nature of ribosomal DNA (rDNA), and especially the possible involvement of RNA polymerase I (RNAPI) in transcription-coupled repair (TCR) have made the study of repair of rDNA both interesting and challenging. TCR, the transcription-dependent, preferential excision repair of the template strand compared with the nontranscribed (coding) strand has been clearly demonstrated in genes transcribed by RNAPII. Whether TCR occurs in rDNA is unresolved. In the present work, we have applied analytical methods to map repair events in rDNA using data generated by the newly developed XR-seq procedure, which measures excision repair genome-wide with single-nucleotide resolution. We find that in human and mouse cell lines, rDNA is not subject to TCR of damage caused by UV or by cisplatin.

Genomic DNA is constantly attacked by a plethora of DNA damaging agents both from endogenous and exogenous sources. Nucleotide excision repair (NER) is the most versatile repair pathway that recognizes and removes a wide range of bulky and/or helix-distorting DNA lesions. Even though the molecular mechanism of NER is well studied through in vitro system, the NER process inside the cell is more complicated because the genomic DNA in eukaryotes is tightly packaged into chromosomes and compacted into a nucleus. Epigenetic modifications regulate gene activity and expression without changing the DNA sequence. The dynamics of epigenetic regulation play a crucial role during the in vivo NER process. In this review, we summarize recent advances in our understanding of the epigenetic regulation of NER.