The role of adenosine triphosphate in the function of human origin recognition complex 4 protein

Abstract

Human origin recognition complex 4 (ORC4) protein, a subunit of the origin recognition complex, belongs to the AAA+ superfamily of adenosine triphosphate (ATP) ases. Proteins belonging to this family require ATP for their function and interactions with ATP lead to conformational changes in them or in their partners. Human ORC4 protein induces structural changes in DNA substrates, promoting renaturation and formation of non-canonical structures, as well as conversion of single-stranded into multi-stranded oligonucleotide structures. The aim of this study was to further investigate the role of ATP in the function of human ORC4 protein. For this purpose, a mutant in the conserved Walker B motif of ORC4, which is able to bind but not to hydrolyze ATP, was constructed and its activity in DNA restructuring reactions was investigated. The obtained results showed that ATP hydrolysis is not necessary for the function of human ORC4. It is proposed that ATP has a structural role as a cofactor in the function of human ORC4 as a DNA restructuring agent.

Keywords

• origin recognition complex (ORC)
• adenosine triphosphate (ATP)
• DNA structure
• origin selection