Telomere

Telomeres, the protective elements at the ends of
chromosomes, need to be maintained for cells to
proliferate indefinitely. In many human cancers, the
telomeric DNA is replenished by telomerase. However, a
second pathway for telomere maintenance, referred to as
the ALT pathway, has increasingly been recognized in
human cancers. The genetic basis for activation of ALT is
not known, but recent data have implicated a chromatin
remodeling complex (ATRX/DAXX) and the histone variant
H3.3 as players in the repression of ALT. We have
examined a large panel of ALT cell lines for their genetic
and cell biological features and found that loss of ATRX is a
common event in the genesis of ALT lines. In addition, we
document that ALT cell lines frequently undergo chromosomal
changes and are impaired in their ability to detect
and repair damage in their DNA. These hallmarks of ALT
are expected to facilitate the detection of ALT–type tumors
in the clinic and may lead to ALT–specific treatments.