This project is aimed at understanding the mechanisms that underlie SINE movement in the mammalian genome. The majority of SINE elements are incapable of efficient amplification, so that the bulk of amplification is dominated by a very few """"""""master"""""""" elements. These active elements are the focus of the current proposal. Model systems include the rodent BC1 gene, which is the ID master sequence, as well as primate Alu and rodent B2 repeats. There are four specific aims: 1) To understand why select SINE loci are capable of active transcription and others are not; 2) To understand the role of different portions of the SINE transcript in the stability of the RNAs; 3) To understand the potential role that RNA-protein interactions play in the stability, transport, and potential amplification of SINEs; 4) To develop a tissue culture system in which to measure the retrotransposition rate from either endogenous Alu elements or exogenously added constructs which have been engineered to increase their retrotransposition rates based on the results of the earlier specific aims. To use this system to study the environmental, genetic and physiological factors that influence SINE mobility.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM045668-06
Application #
2829128
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1993-05-01
Project End
2001-12-31
Budget Start
1998-07-01
Budget End
1998-12-31
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Tulane University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Servant, Geraldine; Streva, Vincent A; Deininger, Prescott L (2017) Transcription coupled repair and biased insertion of human retrotransposon L1 in transcribed genes. Mob DNA 8:18
Servant, Geraldine; Streva, Vincent A; Derbes, Rebecca S et al. (2017) The Nucleotide Excision Repair Pathway Limits L1 Retrotransposition. Genetics 205:139-153
Morales, Maria E; Derbes, Rebecca S; Ade, Catherine M et al. (2016) Heavy Metal Exposure Influences Double Strand Break DNA Repair Outcomes. PLoS One 11:e0151367
Morales, Maria E; White, Travis B; Streva, Vincent A et al. (2015) The contribution of alu elements to mutagenic DNA double-strand break repair. PLoS Genet 11:e1005016
Servant, Geraldine; Deininger, Prescott L (2015) Insertion of Retrotransposons at Chromosome Ends: Adaptive Response to Chromosome Maintenance. Front Genet 6:358
Streva, Vincent A; Jordan, Vallmer E; Linker, Sara et al. (2015) Sequencing, identification and mapping of primed L1 elements (SIMPLE) reveals significant variation in full length L1 elements between individuals. BMC Genomics 16:220
White, Travis B; McCoy, Adam M; Streva, Vincent A et al. (2014) A droplet digital PCR detection method for rare L1 insertions in tumors. Mob DNA 5:30
Ade, Catherine; Roy-Engel, Astrid M; Deininger, Prescott L (2013) Alu elements: an intrinsic source of human genome instability. Curr Opin Virol 3:639-45
Wallace, Nicholas A; Gasior, Stephen L; Faber, Zachary J et al. (2013) HPV 5 and 8 E6 expression reduces ATM protein levels and attenuates LINE-1 retrotransposition. Virology 443:69-79
Streva, Vincent A; Faber, Zachary J; Deininger, Prescott L (2013) LINE-1 and Alu retrotransposition exhibit clonal variation. Mob DNA 4:16

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