Poster Sessions

GENO -31

Rong Guo

R. Guo, D. Xu, A. Sobeck, I. Hickson, M. Hoatlin, W. Wang

RMI2 is a new component of the Bloom syndrome complex and essential for maintaining genome integrity

Mutations in BLM cause Bloom syndrome (BS), which is a rare disorder characterized by growth retardation, genomic instability and cancer predisposition. BLM, BLAP75/RMI1 and Topo 3a form an evolutionarily conserved BLM complex and possess a double holiday junction (DHJ) dissolution activity1,2. The loss of DHJ dissolution activity is believed to be responsible for the genomic instability in BS cells. Here we report a new component of the BLM complex, named RMI2 (for RecQ-Mediated genome Instability 2). RMI2 stably associates with BLM, RMI1 and Topo 3a, and is required for the stability of the BLM complex. RMI2 also co-localizes with BLM and RMI1 in response to DNA damage, and is necessary for BLM and RMI1 to redistribute to nuclear foci in response to DNA damage. Depletion of RMI2 results in reduced phosphorylation level of BLM during mitosis. Importantly, chicken DT40 cells inactivated of RMI2 displays the hallmark feature of Bloom syndrome cells--an increased level of sister-chromatid exchange (SCE). Moreover, DT40 cells inactivated of both RMI2 and BLM exhibited an SCE level comparable to that of BLM-deficient cells. Our data demonstrate that RMI2 is a new essential component of the BLM complex, and participates in the same pathway as BLM in maintaining genome stability.