Determining the mechanisms of normal cell cycle control is critical for our understanding of both development and oncogenesis. During development, cell proliferation occurs by coordinating progress through the cell cycle with growth. Conversely, cell cycle arrest occurs prior to, and is often necessary for, terminal differentiation. Cell proliferation and cell cycle arrest are also highly regulated after the completion of development: stem cells in adult tissues are under tight cell cycle control, as are quiescent cells that only proliferate in response to particular stimuli. Breakdowns in cell cycle control in any of these circumstances can have drastic consequences and contribute to the deregulated growth typical of cancer. The long term objective of this project is to elucidate how developmental programs affect cell cycle progression, a process that remains poorly understood. In this proposal we focus on gene expression mechanisms that control the G1-S transition because this is when most cells decide whether to enter or to exit the cell cycle.

Public Health Relevance

Cell proliferation is a fundamental aspect of the biology of all organisms, and is controlled by a highly orchestrated series of cell biological events termed the cell cycle that directs the accurate duplication and inheritance of the genome. A detailed molecular description of cell cycle events during animal development is critical for our understanding of cell proliferation control, and how such control goes awry in diseases like cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057859-13
Application #
8290570
Study Section
Cellular Signaling and Regulatory Systems Study Section (CSRS)
Program Officer
Hoodbhoy, Tanya
Project Start
1999-01-01
Project End
2013-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
13
Fiscal Year
2012
Total Cost
$294,095
Indirect Cost
$93,174
Name
University of North Carolina Chapel Hill
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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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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Meserve, Joy H; Duronio, Robert J (2012) Atypical E2Fs drive atypical cell cycles. Nat Cell Biol 14:1124-5
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Sloan, Roketa S; Swanson, Christina I; Gavilano, Lily et al. (2012) Characterization of null and hypomorphic alleles of the Drosophila l(2)dtl/cdt2 gene: Larval lethality and male fertility. Fly (Austin) 6:173-83
Burch, Brandon D; Godfrey, Ashley C; Gasdaska, Pamela Y et al. (2011) Interaction between FLASH and Lsm11 is essential for histone pre-mRNA processing in vivo in Drosophila. RNA 17:1132-47
White, Anne E; Burch, Brandon D; Yang, Xiao-Cui et al. (2011) Drosophila histone locus bodies form by hierarchical recruitment of components. J Cell Biol 193:677-94

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