Topoisomerase I inhibitor, Camptothecin, induces apoptosis of human embryonic stem cells

CAROLINA P. GARCIA; GUILLERMO A. VIDELA RICHARDSON; NICOLAS A. DIMOPOULOS; DIEGO A. RIVA; DAMIAN D. FERNANDEZ ESPINOSA; LEONARDO ROMORINI; SANTIAGO G. MIRIUKA; GUSTAVO E. SEVLEVER; MARÍA E. SCASSA

Congreso; ISSCR 11th Annual Meeting; 2013

Human embryonic stem cells (hESC) possess two unique properties that distinguish them from many other cell types: the ability to self-renew indefinitely in culture under permissive conditionsand the capability of giving rise to all cell types of embryonic lineage underthe guidance of appropriate developmental cues (pluripotency). Maintaininggenomic integrity is vital for stem cells and their function as primaryprogenitors, since mutations will severely compromise all derived celllineages. Currently, the mechanisms that protect the genome in rapidlyproliferating hESCs are minimally understood. The pathways controlled by theataxia telangiectasia-mutated (ATM) and ATM-related (ATR) proteins representone of the main pathways by which cells react to DNA damage in somatic cells.In a previous study, we determined that the ATM checkpoint signaling cascade isintact in WA09 hESCs. Here, we investigated how WA09 hESC line reacts toreplication mediated double-strand DNA breaks triggered by the topoisomerase I inhibitor,camptothecin (CPT), and whether this genomic insult evokes DNA repair pathwaysand/or cell death.