HOME ＞ Topics2017 ＞ 11 April 2017

The Ministry of Education, Culture, Sports, Science and Technology (MEXT; Monbu-Kagaku-sho) presents annual prizes to those who have made significant contribution in the field related to science and technology, as special commendation from the Minister of Monbu-Kagaku-sho. Dr. Masai was awarded the 2017 Prize for Science and Technology (Research category) in recognition of his unique and important findings in the mechanisms of genome DNA replication. The prizes are awarded in five categories and the recipients in Research category are those who have conducted unique basic research that would contribute to the development of science and technology in Japan. 

http://www.mext.go.jp/b_menu/houdou/29/04/1384228.htm
　  List of 2017 awardees (PDF ; see page 13)

＜Summary of Dr. Masai’s achievements＞

The inheritance and maintenance of genome is central to all the living creatures on this earth. Thus, DNA replication is the most fundamental and crucial event for the growth and survival of the cells, and is strictly regulated to minimize the genome changes that could lead to various diseases including cancer. 

Dr. Masai used E. coli plasmids as model systems, and analyzed the mechanism of initiation and its regulation. During the course of this work, he discovered replication/ transcription signals on duplex DNA that function only when they are converted to single-stranded DNA. The striking feature of these sequences is their ability to form higher-order structures. More recently, Dr. Masai discovered an essential role of G-quadruplex structure, a non-B type DNA that is formed only when duplex DNA is transiently converted to single-stranded DNA, in regulation of DNA replication in eukaryotes. G4 sequences are recognized by conserved Rif1 protein and facilitate formation of chromatin architecture through Rif1-G4 mediated chromatin association. These studies show the evolutionally conserved importance of DNA with unusual structures as signals for various chromosome transactions, and led Dr. Masai to propose novel functions of genome carried by "shape of DNA”.

Phosphorylation plays a crucial role in regulating DNA replication. Dr. Masai showed that the conserved Cdc7 kinase is a key regulator of initiation of eukaryotic DNA replication, and elucidated the mechanisms of its action at the replication origins. Cdc7 and its substrates Mcm and Claspin regulate initiation of DNA replication by triggering assembly of more complex replisome structures. These proteins can serve as targets of cancer therapy. Indeed, Dr. Masai showed Cdc7 can be an effective target for cancer treatment by developing low molecular inhibitors for this kinase.

Dr. Masai’s findings provided novel insight into the conserved mechanisms of DNA replication and contributed to the development of novel strategies for treatment of cancer and other diseases.

＜Groceries＞

Genome:

The entire body of genomic information carried by each biological species

Protein phosphorylation:

Modification of proteins by covalently linking a phosphate to specific amino acid residues

kinase:

an enzyme that can phosphorylate other proteins

non-B type DNA:

DNA structures distinct from the common right-handed B-type double helix structure

G-qaudruplex (G4):

a type of non-B DNA composed of multiple layers of the "G-quartet”, a planner structure made of four guanines. It is called quadruplex, because four DNA strands are intertwined in G4.

replisome:

a protein complex responsible for DNA synthesis at the replication fork where new DNA chains are synthesized

---

Genome Dynamics Project ▶