Kinetochore/Centromere Integrity and Cancer

Project 3

Failure of accurate chromosome segregation causes CIN (Chromosomal INstability), which includes occurrences of aneuploidy, chromosome breakage, and micronuclei. CIN leads to cancer, various birth defects, as well as up to one third of miscarriage, lethality, and infertility cases.

Aneuploidy is particularly important because it is a hallmark of cancer, especially poor prognosis cancer, as ~90 % of solid tumors show aneuploidy. A major cause of aneuploidy is kinetochore-microtubule attachment errors. One of these errors is lagging chromosome, a kind of “Tug of War” within a sister kinetochore pair by improper microtubule assembly and is often found during anaphase (Figure 4).

Important kinetochore functions include monitoring mitotic errors and error corrections; thus, it is critical to study how the kinetochore ensures the integrity of chromosome segregation. We are studying the mechanism of how the loss of kinetochore integrity causes cancer with a focus on the kinetochore size, the architectural integrity of kinetochores, and the regulation of kinetochore proteins/genes with a focus on colon, breast, and neck cancer.

FRET image of Lagging chromosome in cell