The coordinate regulation of histone protein metabolism with replication of DNA is an important challenge for all organisms. While the cell cycle regulation of histone mRNA in somatic cells is relatively well understood, different mechanisms are used by the early embryo to control the storage and production of histone mRNA for the early cell cycles. Different organisms have solved this problem in distinct ways, and we explore the molecular basis of these different strategies in this proposal. Typically, histone mRNAs are not coordinately regulated with DNA replication in oogenesis and early embryogenesis, but these same mRNAs become cell-cycle regulated sometime after the rapid cleavage phase of embryogenesis. We are studying the molecular basis of this developmental regulation concentrating on two organisms, Xenopus and Drosophila. The key regulatory proteins, SLBPs, bind the 3' end of histone mRNAs. In Xenopus the two SLBPs participate in the storage and translation activation of the histone mRNAs, and using chimeric proteins we are dissecting the molecular function of different parts of each protein. There is a single SLBP in Drosophila, and we are determining how this protein participates in storage of histone mRNA and protein in the developing egg, and then how zygotic synthesis of the protein leads to the development of the normal cell-cycle regulatory pattern of histone mRNA expression. Using genetics, we will identify novel genes involved in biosynthesis and regulation of histone mRNA levels. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM058921-06
Application #
6741433
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Carter, Anthony D
Project Start
1999-05-01
Project End
2007-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
6
Fiscal Year
2004
Total Cost
$326,039
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Biochemistry
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Meserve, Joy H; Duronio, Robert J (2018) Fate mapping during regeneration: Cells that undergo compensatory proliferation in damaged Drosophila eye imaginal discs differentiate into multiple retinal accessory cell types. Dev Biol 444:43-49
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Meserve, Joy H; Duronio, Robert J (2017) A population of G2-arrested cells are selected as sensory organ precursors for the interommatidial bristles of the Drosophila eye. Dev Biol 430:374-384
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Swanson, Christina I; Meserve, Joy H; McCarter, Patrick C et al. (2015) Expression of an S phase-stabilized version of the CDK inhibitor Dacapo can alter endoreplication. Development 142:4288-98

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