DsDNA breaks inflicted by cell-free chromatin particles selectively target telomeres.

Telomere damage can lead to senescence, aging and aging-related disorders, and cancer. Previously, we reported that cell-free chromatin particles (cfChPs) that circulate in human blood can readily enter healthy cells and damage their DNA. Herein, we show that dsDNA breaks inflicted by cfChPs selectively target telomeres, with the resulting DNA damage remaining unrepaired over time, whereas dsDNA breaks inflicted by γ-rays are not specific to telomeres and have a faster repair kinetics. We propose that cfChPs that are released from the billions of dying cells to enter the blood circulation are natural DNA damaging agents with a unique mechanism of action.