Major cutbacks at chromosome ends.

To distinguish a telomere from a double-strand break, a minimum number of telomere repeats must 'cap' each chromosome end. The length of each repeat array will reflect a unique history of addition and losses. Telomere losses are predicted to occur slowly but surely with every replication cycle (referred to as 'typical' telomere loss) in addition to intermittently and, potentially, rapidly ('sporadic'). Recent studies have shown that sporadic telomere losses can result from failure to properly repair (oxidative) damage to telomeric DNA, from failure to properly process higher-order structures of G-rich DNA and from homologous recombination reactions. Differences in telomere-erosion pathways between normal and malignant cells provide novel targets for the prevention and therapy of disease.