NAR Breakthrough - Induction of the alternative lengthening of telomeres pathway by trapping of proteins on DNA
NAR Nucleic Acids Research
Published by Oxford University Press - Impact Factor 16.7
by Anna M Rose, Tomas Goncalves, Siobhan Cunniffe, Helene E B Geiller, Thomas Kent, Sam Shepherd, Malitha Ratnaweera, Roderick J O’Sullivan, Richard J Gibbons, David Clynes
Several types of cancers can divide indefinitely because of their ability to circumvent telomere shortening by mechanisms such as the telomerase-independent, hence Alternative Lengthening of Telomeres (ALT) pathway. The ALT pathway is greatly enhanced in the absence of the ATRX chromatin remodeler. The current study provides evidence that increased amounts of trapped proteins on DNA in the absence of ATRX cause replication forks to collapse, which on telomeres induces ALT. These results may help to better understand tumors with active ALT pathway and may eventually be instrumental in developing new therapeutic strategies.