Loss of RMI2 Increases Genome Instability and Causes a Bloom-Like Syndrome Damien F. Hudson David J. Amor Amber Boys Kathy Butler Lorna Williams Tao Zhang Paul Kalitsis 10.1371/journal.pgen.1006483 https://plos.figshare.com/articles/dataset/Loss_of_RMI2_Increases_Genome_Instability_and_Causes_a_Bloom-Like_Syndrome/4446410 <div><p>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, <i>RMI2</i>, 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 <i>RMI2</i> 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.</p></div> 2016-12-15 18:37:25 replication fork stability FANCD RMI 2 Increases Genome Instability RMI 2 knockout cell lines Bloom-Like Syndrome Bloom syndrome BLM RMI 2 knockout cells chromosome instability phenotypes genome instability III anaphase DNA bridges sister chromatid exchange gene