Damage to mitotic telomeres results in DNA damage response activation, cell division delay, and micronucleation (548.1)

Telomeres are nucleoprotein structures required to protect chromosome ends. Uncapping of telomeres during interphase elicits a DNA damage response causing cell cycle arrest, aberrant DNA damage repair resulting in, chromosomal end fusion, chromosome instability and eventually lead to tumorigenesis. In the present study we investigate the consequences of DNA damage occurring at telomeres during the mitotic phase of the cell cycle using laser microirradiation. Microirradiation was used in combination with GFP live-cell imaging and dual-labeling to study double-strand break (DSB) repair by monitoring the co-localization of γH2AX with DNA damage response (DDR) factors. We found DDR proteins such as ATM and WRN localize to damaged telomeres but not to other chromosomal sites of focal laser damage. Interestingly, damage at mitotic telomeres results in a delay in anaphase onset, which is dependent on the activity of ATM, Chk1 and the spindle assembly checkpoint kinase, Mps1. Telomere-damaged cells exited mitosis...