Investigating the Interaction of RecQL4 and Mcm10 in Drosophila melanogaster

Abstract

Accurate duplication and regulation of the eukaryotic genome requires precise coordination among multiple replication factors. RecQL4, the least characterized RecQ protein, is a 1208 amino acid protein containing a centrally located and highly conserved helicase domain. Mutations in RecQL4 may lead to distinct clinical diseases with premature aging symptoms and increased cancer rates. Recently, efforts have focused on elucidating specific protein-protein interactions to shed light into the cellular processes in which RecQL4 may be involved. Previously, others have shown a direct interaction between RecQL4 and Mini-chromosome-maintenance protein 10 (Mcm10), a highly conserved protein with essential roles in DNA replication and heterochromatin formation. Work in 293T cells suggests that Mcm10 mediates the association of RecQL4 with the Mcm2-7 helicase; however, the biological ramifications of this interaction in a multicellular context remain unclear. Using both yeast two-hybrid and genetic approaches, we have shown that the RecQL4-Mcm10 interaction is conserved in Drosophila melanogaster and is important for alternate modes of replication. This study highlights the key roles of RecQL4 and Mcm10 in cell viability and further demonstrates their cooperative function in DNA replication.