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