Abstract
Chromosome instability usually leads to tumorigenesis. Bloom syndrome (BS) is a genetic disease associated with chromosome instability. The BS gene product, BLM, has been reported to function in the spindle assembly checkpoint (SAC) to prevent chromosome instability. BTR complex, composed of BLM, topoisomerase IIIα (Topo IIIα), RMI1 (RecQ-mediated genome instability protein 1, BLAP75) and RMI2 (RecQ-mediated genome instability protein 2, BLAP18), is crucial for maintaining genome stability. Recent work has demonstrated that RMI2 also plays critical role in SAC. However, little is know about RMI1 regulation during the cell cycle. Here we present that RMI1 protein level does not change through G1, S and G2 phases, but significantly increases in M phase. Moreover, phosphorylation of RMI1 occurs in mitosis. Upon microtubule-disturbing agent, RMI1 is phosphorylated primarily at the sites of Serine 284 and Serine 292, which does not interfere with the formation of BTR complex. Additionally, this phosphorylation is partially reversed by roscovitine treatment, implying cycling-dependent kinase 1 (CDK1) might be one of the upstream kinases.
Highlights
Bloom syndrome (BS) is a severe chromosome instability disease characterized by predisposition to a wide range of cancers and around 10-fold elevation of sister chromatid exchanges (SCEs) frequency in BS cells [1,2]
RMI1 (RecQ-Mediated Genome Instability Protein 1) Protein Level Remains Unchanged through the Cell Cycle G1 to G2 Phase
Given that BLM protein level is cell cycle-regulated, we examined whether there are any cell cycle-specific changes in RMI1 expression level by using synchronized cells at various cell cycle stages
Summary
Bloom syndrome (BS) is a severe chromosome instability disease characterized by predisposition to a wide range of cancers and around 10-fold elevation of sister chromatid exchanges (SCEs) frequency in BS cells [1,2]. The list of BLM protein partners is becoming progressively lengthier, it was found that BLM only has three consistent protein partners, Topo IIIα (topoisomerase IIIα), RMI1 (RecQ-mediated genome instability protein 1, BLAP75), and RMI2 (RecQ-mediated genome instability protein 2, BLAP18), which form a BTR complex with BLM [12,13,14]. Both RMI1 and RMI2 contain OB-fold (oligonucleotide/oligosaccharide binding) domain. The fluctuating BLM protein level is consistent with BLM functions in DNA replication, homologous recombination, and preventing sister chromatid exchanges, since all of these events could only occur in S, G2, and M phases. Our studies reveal that RMI1 is phosphorylated with similar kinetics to BLM during mitosis, with two major phosphorylation sites, Ser284 and Ser292
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