TRIGGERING ALT: Knocking down ASF1 launches cells into the alternative lengthening of telomeres (ALT) response. Replication protein A2 (RPA2) appears in promyelocytic leukemia (PML) bodies, as do repeats of linear and circular telomeric DNA with the sequence TTAGGG (1). Also in ALT, telomere recombination is associated with PML bodies (2) and the length of telomeres becomes more variable (3).
The paper
R.J. O’Sullivan et al., “Rapid induction of alternative lengthening of telomeres by depletion of the histone chaperone ASF1,” Nat Struct Mol Biol, 21:167-74, 2014.
Cancer cell immortality hinges on telomeres, the caps of repetitive DNA that protect the ends of chromosomes. Every time a normal cell divides, its telomeres shorten, and eventually the cell’s telomeres are so short that it stops dividing or self-destructs. Most cancer cells can divide indefinitely because they upregulate telomerase—an enzyme that lengthens telomeres—but 5 to 15 percent of cancers use a pathway called alternative lengthening of telomeres (ALT) to avoid apoptosis.
One of the hallmarks of ALT is the accumulation of replication protein A2 (RPA2) in specialized areas of the nucleus called promyelocytic leukemia (PML) bodies, named after ...
