A Double Holliday Junction Dissolvasome Comprising BLM, Topoisomerase IIIα, and BLAP75 *

摘要: Bloom syndrome (BS), an autosomal recessive disorder, is marked by a high incidence of cancer early in life. Cells derived from BS patients are unstable genetically and exhibit frequent sister chromatid exchanges, reflective homologous recombination (HR) deregulation. BLM, the RecQ-like helicase mutated BS, found several cellular protein complexes, all which contain topoisomerase IIIα (Topo IIIα) novel BLAP75. Here, using highly purified human proteins, we show that BLAP75 associates independently with both Topo BLM. Even though BLM can dissolve double Holliday junction (DHJ) to yield non-crossover recombinants (1), under physiological conditions, DHJ dissolution becomes completely dependent on The effect BLM-Topo specific, as it not seen combination Escherichia coli RecQ or another WRN. Thus, IIIα, constitute dissolvasome complex processes HR intermediates limit DNA crossover formation. This function IIIα-BLAP75 likely indispensable for genome maintenance avoidance.