Loss of RMI2 destabilises the BLM complex in Bloom-like syndrome — ASN Events
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  3. Loss of RMI2 destabilises the BLM complex in Bloom-like syndrome

Loss of RMI2 destabilises the BLM complex in Bloom-like syndrome (#184)

Paul Kalitsis 1 2 , David J Amor 1 2 , Amber Boys 3 , Kathy Butler 3 , Lorna Williams 3 , Tao Zhang 1 , Damien Hudson 1 2
  1. Murdoch Childrens Research Institute, Parkville, VICTORIA, Australia
  2. Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia
  3. Cytogenetics Laboratory, Victorian Clinical Genetics Services, Parkville, Victoria, Australia

Bloom syndrome is a recessive human genetic disorder with features of genome instability, growth deficiency and predisposition to cancer. The only known causative gene is the BLM helicase that is a member of a protein complex along with topoisomerase III alpha, RMI1 and 2, which maintains replication fork stability and dissolves double Holliday junctions to prevent genome instability. Here we report the identification of a second gene, RMI2, that is deleted in affected siblings with Bloom-like features. Cells from homozygous individuals exhibit elevated rates of sister chromatid exchange, anaphase DNA bridges and micronuclei. Similar genome and chromosome instability phenotypes are observed in independently derived RMI2 knockout cells. In both patient and knockout cell lines reduced localisation of BLM to ultra fine DNA bridges and FANCD2 at foci linking bridges are observed. Overall, loss of RMI2 produces a partially active BLM complex with mild features of Bloom syndrome.

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