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PMID: 15454538 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

SNR1 (INI1/SNF5) mediates important cell growth functions of the Drosophila Brahma (SWI/SNF) chromatin remodeling complex.

Genetics ·Vol. 168 ·No. 1 ·2004-09-00 ·Pages 199-214

Zraly CB, Marenda DR, Dingwall AK

Abstract

SNR1 is an essential subunit of the Drosophila Brahma (Brm) ATP-dependent chromatin remodeling complex, with counterparts in yeast (SNF5) and mammals (INI1). Increased cell growth and wing patterning defects are associated with a conditional snr1 mutant, while loss of INI1 function is directly linked with aggressive cancers, suggesting important roles in development and growth control. The Brm complex is known to function during G1 phase, where it appears to assist in restricting entry into S phase. In Drosophila, the activity of DmcycE/CDK2 is rate limiting for entry into S phase and we previously found that the Brm complex can suppress a reduced growth phenotype associated with a hypomorphic DmcycE mutant. Our results reveal that SNR1 helps mediate associations between the Brm complex and DmcycE/CDK2 both in vitro and in vivo. Further, disrupting snr1 function suppressed DmcycEJP phenotypes, and increased cell growth defects associated with the conditional snr1E1 mutant were suppressed by reducing DmcycE levels. While the snr1E1-dependent increased cell growth did not appear to be directly associated with altered expression of G1 or G2 cyclins, transcription of the G2-M regulator string/cdc25 was reduced. Thus, in addition to important functions of the Brm complex in G1-S control, the complex also appears to be important for transcription of genes required for cell cycle progression.

MeSH Terms
Animals CDC2-CDC28 Kinases/metabolism Cell Cycle/physiology Cell Cycle Proteins/genetics Cell Growth Processes/genetics,physiology Chromatin Assembly and Disassembly/genetics Cyclin-Dependent Kinase 2 Drosophila Proteins/genetics,metabolism,physiology Drosophila melanogaster/genetics Electrophoresis, Polyacrylamide Gel Fluorescent Antibody Technique G1 Phase/genetics,physiology Gene Expression Regulation, Developmental Glutathione Transferase Mutation/genetics Phenotype Protein Tyrosine Phosphatases/metabolism Reverse Transcriptase Polymerase Chain Reaction Trans-Activators/genetics Transcription Factors/genetics,metabolism,physiology Wings, Animal/anatomy & histology
Chemicals
Cell Cycle Proteins Drosophila Proteins Snr1 protein, Drosophila Trans-Activators Transcription Factors brm protein, Drosophila Glutathione Transferase CDC2-CDC28 Kinases Cyclin-Dependent Kinase 2 cdk2 protein, Drosophila Protein Tyrosine Phosphatases stg protein, Drosophila
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Zraly Claudia B
Oncology Institute, Cardinal Bernardin Cancer Center, Stritch School of Medicine, Loyola University of Chicago, Maywood, Illinois 60153, USA.
Marenda Daniel R
Dingwall Andrew K
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Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
0016-6731
DOI
10.1534/genetics.104.029439
Published
2004-09-00
Pages
199-214
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC1448117
Subset
IM
External Links
PubMed source DOI: 10.1534/genetics.104.029439 PMC Full Text View journal details
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