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BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates

Wu, L., Bachrati, C. Z., Ou, J., Xu, C., Yin, JH., Chang, M., Wang, W., Li, L., Brown, GW. & Hickson, ID., 14-Mar-2006, In : Proceedings of the National Academy of Sciences of the United States of America. 103, 11, p. 4068-4073 6 p.

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  • Leonard Wu
  • Csanad Z. Bachrati
  • Jiongwen Ou
  • Chang Xu
  • JH Yin
  • M Chang
  • Weidong Wang
  • Lei Li
  • GW Brown
  • ID Hickson

BLM encodes a member of the highly conserved RecQ DNA helicase family, which is essential for the maintenance of genome stability. Homozygous inactivation of BLM gives rise to the cancer predisposition disorder Bloom's syndrome. A common feature of many RecQ helicase mutants is a hyperrecombination phenotype. In Bloom's syndrome, this phenotype manifests as an elevated frequency of sister chromatid exchanges and interhomologue recombination. We have shown previously that BLM, together with its evolutionarily conserved binding partner topoisomerase Ilia (hTOPO III alpha), can process recombination intermediates that contain double Holliday junctions into noncrossover products by a mechanism termed dissolution. Here we show that a recently identified third component of the human BLM/hTOPO III alpha complex, BLAP75/RMI1, promotes dissolution catalyzed by hTOPO III alpha. This activity of BLAP75/RMI1 is specific for dissolution catalyzed by hTOPO III alpha because it has no effect in reactions containing either Escherichia coli Top1 or Top3, both of which can also catalyze dissolution in a BLM-dependent manner. We present evidence that BLAP75/RMI1 acts by recruiting hTOPO III alpha to double Holliday junctions. Implications of the conserved ability of type IA topoisomerases to catalyze dissolution and how the evolution of factors such as BLAP75/RMI1 might confer specificity on the execution of this process are discussed.

Original languageEnglish
Pages (from-to)4068-4073
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number11
Publication statusPublished - 14-Mar-2006
Externally publishedYes

    Keywords

  • Bloom's syndrome, Holliday junction dissolution, topoisomerase III, sister chromatid exchanges, SYNDROME GENE-PRODUCT, SISTER-CHROMATID EXCHANGES, WERNERS-SYNDROME GENES, TOPOISOMERASE-III, RECQ HELICASES, BLOOM-SYNDROME, SCHIZOSACCHAROMYCES-POMBE, SACCHAROMYCES-CEREVISIAE, HOLLIDAY JUNCTIONS, REPLICATION FORKS

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