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Jill M. Schumacher, Ph.D. 1995, University of Washington The University of Texas M. D. Anderson Cancer Center |
Research Interests:
Our research
is focused on the regulation of chromosome dynamics during the eukaryotic
cell cycle. For these studies, we utilize genetic, biochemical, and cell biological
methods using the soil nematode, C. elegans, as a model system. We
have concentrated our efforts on two members of a highly conserved family
of proteins, the Aurora kinases. In the past decade years, the Aurora kinases
have emerged as critical mitotic regulatory proteins that contribute to multiple
tumor types in man. The identification of the substrates and regulators of
these kinases is our current goal.
The C. elegans Aurora A kinase AIR-1 and Aurora B kinase AIR-2 are
each uniquely localized to the mitotic spindle and are required at different
times during the cell cycle. The AIR-1 protein is associated with mitotic
centrosomes and is required early in mitosis for the proper assembly and function
of the mitotic spindle. The AIR-2 protein is initially localized to metaphase
chromosomes and translocates to the central spindle microtubules at anaphase.
AIR-2 is required for appropriate kinetochore/microtubule attachments and
for the organization of the central spindle, a structure that is essential
for the completion of cytokinesis.
My lab has recently identified two highly conserved activators of the Aurora
B kinase, INCENP and the Tousled kinase. Although INCENP clearly has a role
in mitotic chromosome segregation, Tousled has been implicated in chromatin
assembly and transcription. We hypothesize that each activator/Aurora B complex
may have a distinct subset of substrates that are involved in specific aspects
of chromosome dynamics. We are now undertaking molecular and genetic screens
to find such substrates.
A separate project in the lab is focused on the role of AIR-1 and its substrates
in germ cell development. AIR-1 is required for germ cell proliferation and
phosphorylates a kinase, GCK-1, that is required for appropriate progression
of the meiotic cell cycle. Interestingly, GCK-1 localizes to P-bodies in the
C. elegans germ line and early embryo. P-bodies have recently emerged
as key players in RNA processing and RNA mediated interference. We are currently
addressing the role of GCK-1 and AIR-1 in P-body functions and germline development.
Selected publications:
Reifler GM, Dent SYR, Schumacher JM (2008) Tousled-Mediated Activation
of Aurora B Kinase Does Not Require Tousled Kinase Activity In Vivo. J Biol
Chem 283:12763-12768.
Zhang K, Lin W, Latham JA, Riefler GM, Schumacher JM, Chan CS, Tatchell K, Hawke
DH, Kobayashi R, SYR Dent (2005) The Set1 methyltransferase opposes Ipl1 Aurora
kinase functions in chromosome segregation. Cell 122:723-734.
Han Z, Riefler GM, Saam JR, Mango SE, Schumacher JM (2005) The C. elegans Tousled-like
kinase contributes to chromosome segregation as a substrate and regulator of
the Aurora B kinase. Curr Biol 15:894-904. A dispatch article on this paper
appeared in Curr Biol 15:R379-382.
Han Z, Saam JR, Adams HP, Mango SE, Schumacher JM (2003) The C.elegans Tousled-like
kinase (TLK-1) has an essential role in transcription. Curr Biol 13:1921-1929.
A dispatch article on this paper appeared in Curr Biol 13:R915-916.
Program Affiliation:
Program in Genes and
Development