New insights into the centromere structure

Osaka University researchers used cryogenic electron microscopy for analysis of the atomic structure in the centromeric region on the chromosome. This is critical for cell division. Researchers discovered that the centromere is marked by a protei...

Osaka University researchers used cryogenic electron microscopy analysis for a structural change analysis of the centromere at atomic level during cell divide

Osaka, Japan - Cells' genetic material is organized into structures called "chromosomes".The centromere is vital for proper division of the chromosomes through interaction with spindle micrtubules during cell division and growth. Researchers at Osaka University have now clarified the structure and function of the centromere in chicken cells by using cryogenic electron microscopy (cryoEM).

CryoEM freezes samples quickly to preserve them and stabilize them. Then, images are taken using collisions of electrons to reveal the structure. The centromeric region is home to a complex of proteins known as the "kinetochore", which is vital for proper cell division. Cryo-EM analysis was used to reveal a structural change in the kinetochore.

When DNA is condensed into the chromosomes it is wrapped around a core of proteins called histones to form what is known as a nucleosome. The centromeric region contains a variant of the histone protein CENP-A. This protein specifies the centromere's location. The mechanism by which CENPA is deposited at centromeres to accurately define their location was not known until now.

The research team discovered that CENP-C, a protein known as mitosis (the process by which cells divide), binds to CENP-A and acts like a scaffold for other Kinetochore proteins. Interphase, when cells are not dividing, is when a different protein called KNL2 bonds to centromeres. Honghui Jiang, Mariko Ariyoshi, and Mariko Ariyoshi, the study's lead authors, explain that KNL2 has a CENP–C-like motif and is part of the Mis18 complex. This licensing factor allows for new CENP–A deposition.

Further, the team discovered that the interaction between KNL2 & the centromere is necessary for new deposition CENP-A during interphase. This in turn helps to maintain the correct position of the centromere. Tatsuo Fukagawa, senior author, explains that CENPC is phosphorylated in mitosis and that phosphorylated CENPC excludes KNL2 form the KNL2-CENP–A complex. This suggests that KNL2 binds CENP-A via interphase, keeping the centromere in place until a phosphate mole becomes bound to CENPC as the cells reach the mitotic stage. CENP-C then preferentially binds CENP-A, allowing for the formation of the cell division kinetochore.

These new insights into the structure and function of the centromeric region are crucial for understanding cell division and growth. Anti-cancer drugs can target proteins involved in cell division as well as the kinetochore. This research will also help to design new drugs for cancer.