Telomere uncapping at the crossroad between cell cycle arrest and carcinogenesis.
Telomeres are nucleoprotein complexes that protect the natural ends of chromosomes from fusion and degradation and prevent them eliciting a checkpoint response. This protective function, which is called telomere capping, is largely mediated by telomere-binding proteins that suppress checkpoint activation and DNA repair activities. Telomere dysfunction through progressive shortening or removal of capping proteins leads to a checkpoint-mediated block of cell proliferation, which acts as a cancer-suppressor mechanism. However, genetic alterations that inactivate the checkpoint can lead to further telomere erosion and increased genomic instability that, coupled with the activation of mechanisms to restabilize telomeres, can drive the oncogenic process.
Dipartimento di Biotecnologie e Bioscienze; Università degli Studi di Milano-Bicocca; Milano, Italia.
Elisa
E
Gobbini
Dipartimento di Biotecnologie e Bioscienze; Università degli Studi di Milano-Bicocca; Milano, Italia.
Camilla
C
Trovesi
Dipartimento di Biotecnologie e Bioscienze; Università degli Studi di Milano-Bicocca; Milano, Italia.
Corinne
C
Cassani
Dipartimento di Biotecnologie e Bioscienze; Università degli Studi di Milano-Bicocca; Milano, Italia.
Maria Pia
MP
Longhese
cancer; checkpoint; double-strand breaks; genomic stability; telomere