Geminin as an Emerging Anticancer Drug Target

Abstract

For normal cell division, one time replication origin firing is mandatory. The mutual interaction and levels of Cdt1 and geminin (GMNN) proteins are known to be involved in this regulatory mechanism. Imbalance between these protein levels may cause defects in replication of DNA leading to genome instability. This might cause cancer. In different stem cells, such as leukemic and hematopoietic stem cells, significant levels of GMNN have been recorded. It has been observed that siRNA mediated GMNN suppression can arrest cancer cell proliferation without affecting the normal cells. Two molecules of GMNN and one molecule of Cdt1 form a heterotrimer, and two heterotrimer combines and form heterohexamer which inhibits the DNA licensing process. Any moiety that is able to inhibit the formation of GMNN-Cdt1 heterohexamer might act as regulatory source and could be utilized as a DNA replication inhibitor in cancer cells