Accurate chromosome segregation during mitosis is necessary to prevent genetic instability and aneuploidy that are associated with cancer and many types of birth defects. Central to nearly all mitotic events are kinetochores, which are large proteinaceous structures located at the primary constriction, or centromere region, of mitotic chromosomes. Kinetochores are the sites where microtubules of the mitotic spindle attach to chromosomes, and they are responsible for producing force at this attachment site for chromosome movements during mitosis. Kinetochores also function to monitor these attachments and activate a cell-cycle checkpoint which inhibits anaphase onset until all chromosomes are properly bi-oriented and aligned at the metaphase plate.

Research in this lab will focus on understanding how the vertebrate kinetochore accomplishes these remarkable tasks during mitosis using a combination of cell biological, biochemical, and proteomic approaches, with special emphasis on high resolution light microscopy. Current studies are focused on the role of the highly conserved Ndc80 complex in kinetochore-microtubule attachment and regulation of chromosome movement. In addition, we are studying how protein kinases at the vertebrate kinetochore contribute to accurate chromosome segregation in mitosis.

Deluca JG, Gall WE, Ciferri C, Cimini D, Musacchio A, Salmon ED. 2006. Kinetochore microtubule dynamics and attachment stability are regulated by Hec1. Cell. 127(5):969-82

DeLuca JG, Dong Y, Hergert P, Strauss J, Hickey JM, et al. 2005. Hec1 and Nuf2 are core components of the kinetochore outer plate essential for organizing microtubule attachment sites. Molecular Biology of the Cell 16: 519-31

Ciferri C, DeLuca J, Monzani S, Ferrari KJ, Ristic D, Wyman C, Stark H, Kilmartin J, Salmon ED, Musacchio A. 2005. Architecture of the human Ndc80-Hec1 complex, a critical constituent of the outer kinetochore. Journal of Biological Chemistry 280:29088-95.

Salmon ED, Cimini D, Cameron LA, DeLuca JG. 2005. Merotelic kinetochores in mammalian tissue cells. Philos Trans R Soc Lond B Biol Sci. 360:553-68.

DeLuca JG, Salmon ED. 2004. Kinetochores: if you build it, they will come. Current Biology 14: R921-3

Maiato H, DeLuca J, Salmon ED, Earnshaw WC. 2004. The dynamic kinetochore-microtubule interface. Journal of Cell Science 117: 5461-77

DeLuca JG, Howell BJ, Canman JC, Hickey JM, Fang G, Salmon ED. 2003. Nuf2 and Hec1 are required for retention of the checkpoint proteins Mad1 and Mad2 to kinetochores. Current Biology 13: 2103-9

DeLuca JG, Moree B, Hickey JM, Kilmartin JV, Salmon ED. 2002. hNuf2 inhibition blocks stable kinetochore-microtubule attachment and induces mitotic cell death in HeLa cells. Journal of Cell Biology 159: 549-55

Newton CN, DeLuca JG, Himes RH, Miller HP, Jordan MA, Wilson L. 2002. Intrinsically slow dynamic instability of HeLa cell microtubules in vitro. Journal of Biological Chemistry 277: 42456-62

DeLuca JG, Newton CN, Himes RH, Jordan MA, Wilson L. 2001. Purification and characterization of native conventional kinesin, HSET, and CENP-E from mitotic HeLa cells. Journal of Biological Chemistry 276: 28014-21