DNA end joining becomes less efficient and more error-prone during cellular senescence

DNA end joining becomes less efficient and more error-prone during cellular senescence.

Accumulation of somatic mutations is thought to contribute to the aging process. Genomic instability has been shown to increase during aging, suggesting an aberrant function of DNA double-strand break (DSB) repair. Surprisingly, DSB repair has not been examined with respect to cellular senescence. Therefore, we have studied the ability of young, presenescent, and senescent normal human fibrobla...

Lung Basal Stem Cells Rapidly Repair DNA Damage Using the Error-Prone Nonhomologous End-Joining Pathway

Lung squamous cell carcinoma (SqCC), the second most common subtype of lung cancer, is strongly associated with tobacco smoking and exhibits genomic instability. The cellular origins and molecular processes that contribute to SqCC formation are largely unexplored. Here we show that human basal stem cells (BSCs) isolated from heavy smokers proliferate extensively, whereas their alveolar progenit...

Introduction: When More Becomes Less

Error-prone nonhomologous end joining repair operates in human pluripotent stem cells during late G2

Genome stability of human embryonic stem cells (hESC) is an important issue because even minor genetic alterations can negatively impact cell functionality and safety. The incorrect repair of DNA double-stranded breaks (DSBs) is the ultimate cause of the formation of chromosomal aberrations. Using G2 radiosensitivity assay, we analyzed chromosomal aberrations in pluripotent stem cells and somat...

When becomes more in fact less?

The principles ‘in dubio abstine’ and ‘primum non nocere’ are as least as old as the language they are written in, and have been made very concrete in criticisms on iatrogenesis, medicalization, polypharmacy and polypragmasy. Clinical decision analysis [1], health technology assessment, and critical appraisal of clinical evidence [2] have provided useful methods to translate these principles in...