Discovery and nomenclature

The full-length cDNA of C16orf75 was first cloned, sequenced and deposited by the National Institutes of Health Mammalian Gene Collection (MGC) program team (MGC24665) [1]. The gene corresponding to MGC24665 cDNA was named C16orf75 suggesting it is a putative ORF number 75 located on chromosome 16 [2]. The protein encoded by C16orf75 was first identified as a component of the BLM protein complex independently by two different groups [3][4]. The protein was named as BLAP18 (BLM-associated polypeptide of 18 kDa mass) or RMI2 (RecQ-mediated genome instability 2)[3][4].

Structure

• RMI2 is a 147 amino acid protein with a predicted molecular weight of 15.9 kDa [3][4].
• RMI2 had an apparent molecular mass of 18 to 20 kD by SDS-PAGE [3][4].
• RMI2 contains a putative OB-fold domain. The OB-fold domain of RMI2 is more similar to the OB-fold domain "D" in RPA2 [3][4].

Orthologs

• RMI2 orthologs have been found in vertebrates and plants and absent in invertebrates and yeast [4].

Interactions

• RMI2 interacts with RMI1 through OB-fold domains [4]. RMI2 promotes the proper folding of RMI1 [4].
• RMI2 exists in complex with BLM, Topo IIIα and RMI1 [3][4] RMI2 is clearly one of the prominent polypeptide component of the purified BLM complex [3].
• Immunoprecipitation of RMI2 using an anti-RMI2 antibody revealed the presence of BLM, Topo IIIα and RMI1 in the purified complex [3].
• RMI2 was coimmunoprecipitated by antibodies against multiple components of the BLM complex, including BLM, RMI1, RPA32, and RPA70 [Ref].
• The formation of a stable RMI2, RMI1 and Topo IIIα complex can occur in the absence of BLM [3].
• The interaction of RMI2 with BLM increases after DNA damage or replication block [3].

Function

• Depletion of RMI2 using siRNA results in the destabilization of the BTB complex (BLM–Topo IIIa–BLAP75/RMI1) [3].
• RMI2 is required for the stability of Topo IIIα and RMI1 [3].
• RMI2-depleted cells show spontaneous chromosomal breaks [3].
• RMI2-depleted cells are sensitive to methyl methanesulfonate treatment [3].
• RMI2 is required to target BLM to chromatin in response to replication block [3].
• RMI2 is required for the assembly of BLM foci upon hydroxyurea treatment [3].
• RMI2 enhances the double Holliday junction (dHj) dissolution capability of BLM, Topo IIIα and RMI1 complex [3].
• BLM phosphorylation is reduced in cells depleted of RMI2 [4].

Secondary modifications

• RMI2 is phosphorylated during mitosis [3].

References