Genome instability is central to carcinogenesis but also is a factor in some neurodegenerative diseases such as amyotrophic lateral sclerosis or the neuromuscular disease. DNA double-strand breaks are generally repaired in the context of highly organized chromatin. It has become clear that the chromatin environment plays an important role in DNA damage response.
Compared with the two types of DNA lesions, DNA double-strand breaks (DSBs) are particularly dangerous to cells because failure to repair these kinds of damage in an appropriate manner can cause cell death, and aberrant repair can lead to gross chromosomal abnormalities that may eventually lead to tumorigenesis.
The two deeply studied DSB repair pathways are homologous recombination (HR) and nonhomologous end-joining (NHEJ). In NHEJ, the DSB ends are blocked from 5′ end resection and held in a close proximity by DSB end-binding protein complex, the Ku70–Ku80 heterodimer. HR is largely error free and is initiated when the DSB is resected by nucleases and helicases.
A number of epigenetic regulators that physically or chemically modify chromatin structures have been linked to DSB repair. This study indicates that KDM5B becomes enriched in DNA-damage sites after ironizing radiation and endonuclease treatment in a poly (ADP ribose) polymerase 1- and histone variant macroH2A1.1dependent manner.
This work provides evidence to indicate that KDM5B is an important genome caretaker and a critical regulator of genome stability.