Knock-In Reporter Mice Demonstrate that DNA Repair by Non-homologous End Joining Declines with Age

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DNA damage disrupting both DNA strands, termed double strand breaks (DSBs), poses a threat to cell survival. If repaired inappropriately, such DNA breaks lead to genomic rearrangements, mutations, and ultimately cancer. Nonhomologous end joining (NHEJ) is the major pathway for repairing double-stranded breaks in mammals. Errors associated with NHEJ have been implicated in the aging process because mice with mutations in NHEJ genes exhibit premature aging. It remains unknown, however, whether NHEJ becomes impaired during normal aging. Studies of age-related changes in NHEJ have been hampered by the lack of a mouse model that would allow detection and quantification of NHEJ events. Here we report generation of NHEJ reporter mice containing a GFP-based NHEJ cassette knocked-into the ROSA26 locus. Using this mouse model, we were able to compare NHEJ across different tissues and demonstrate that NHEJ becomes less efficient and more error-prone with age. Our results provide a mechanism for age-related genomic instability and increased cancer incidence with age. The NHEJ reporter mice will be useful for a broad range of studies in the fields of aging and DNA repair.

Vyšlo v časopise: Knock-In Reporter Mice Demonstrate that DNA Repair by Non-homologous End Joining Declines with Age. PLoS Genet 10(7): e32767. doi:10.1371/journal.pgen.1004511
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004511

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