ALT cells are typified by the presence of ALT-associated PML bodies that include telomeric DNA and telomeric proteins. Although the functions of APBs are unclear, they are considered primary sites of telomere metabolism. Aberrant telomere metabolism results in telomere dysfunction, yield chromosomal abnormalities, such as chromosome end-to-end fusions, telomeric translocations, tri- and quadri-radial chromosomes, and limit growth potential. The mechanisms of ALT remain unclear. However, several DNA damage response proteins are implicated in ALT due to their association with telomeres or APBs, including the recQ-like helicases BLM and WRN, and the tumor suppressor BRCA1. BLM inhibits recombination by facilitating the resolution of recombination and replication intermediates. Through its structure-specific unwinding activity, BLM helps to resolve DNA damage-induced replication blocks that if left unresolved will result in aberrant recombination and chromosomal breakage. BLM ML281 associates with numerous proteins involved in DNA repair including BRCA1, DNA topoisomerases, DNA mismatch repair proteins and Fanconi anemia proteins, and is a component of the BRCA1-associated genome surveillance complex. BLM also associates with several telomerespecific proteins, such as POT1, TRF1 and TRF2. Biochemically, POT1 stimulates BLM unwinding of telomeric DNA end structures including D-loops and Baicalein G-quadruplexes during DNA replication and/or recombination. TRF1 and TRF2 also modulate BLM function using telomeric substrates. The role of BLM in telomere metabolism is emphasized by telomere dysfunction in cells from those with Bloom��s syndrome or cells lacking BLM, including increased telomeric associations and increased frequency of anaphase bridges involving telomeres. While BLM plays a major role in regulating genomic sister chromatid exchange, studies investigating telomeric sister chromatid exchange in cells lacking BLM have yielded inconsistent results but do not support a major role for BLM in regulating T-SCEs in ALT cells.The tumor suppressor BRCA1 performs a key role in the cellular DNA-damage response and recombination repair by promoting both homologous recombination and non-homologous end-joining.