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The Drosophila heterochromatic gene encoding poly(ADP-ribose) polymerase (PARP) is required to modulate chromatin structure during development
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Poly(ADP-ribose) polymerase (PARP) is a major NAD-dependent modifying enzyme that mediates important steps in DNA repair, transcription, and apoptosis, but its role during development is poorly understood. We found that a single Drosophila Parp gene spans more than 150 kb of transposon-rich centromeric heterochromatin and produces several differentially spliced transcripts, including a novel isoform, PARP-e, predicted to encode a protein lacking enzymatic activity. An insertion mutation near the upstream promoter for Parp-e disrupts all Parp expression. Heterochromatic but not euchromatic sequences become hypersensitive to micrococcal nuclease, nucleoli fail to form, and transcript levels of the copia retrotransposon are elevated more than 50-fold; the variegated expression of certain transgenes is dominantly enhanced. Larval lethality can be rescued and PARP activity restored by expressing a cDNA encoding PARP-e. We propose that PARP-e autoregulates Parp transcription by influencing the chromatin structure of its heterochromatic environment. Our results indicate that Parp plays a fundamental role organizing the structure of Drosophila chromatin.
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“a protein which has been implicated in the silencing of retrotransposons in Drosophila30”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [30]
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Metadata
- Authors
- Tulin, A., Stewart, D., & Spradling, A. C.
- Affiliations
- Carnegie Institution for Science (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2002-08-15
- Volume
- 16
- Issue
- 16
- Pages
- 2108-2119
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC186441
- OpenAlex
- W2128974910
- Cited by
- 204
- References
- 53
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 8 · 2023: 8 · 2022: 6 · 2021: 4 · 2020: 3 · 2019: 5 · 2017: 1 · 2016: 10 · 2015: 3 · 2014: 10 · 2013: 10 · 2012: 9
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences (GM-27875)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- poly(ADP-ribose) polymerase, Drosophila, centromeric heterochromatin, chromatin structure, alternative splicing, nucleolus formation, copia retrotransposon, developmental lethality
- MeSH terms
- Animals, Cell Nucleolus, Chromatin, Chromosome Mapping, Chromosomes, DNA, DNA Transposable Elements, Drosophila, Genes, Dominant, Genotype, Heterochromatin, Immunohistochemistry, Micrococcal Nuclease, Microscopy, Fluorescence, Models, Genetic, Mutation, Poly(ADP-ribose) Polymerases, RNA, Messenger, Time Factors, Blotting, Northern, In Situ Hybridization, Fluorescence, DNA, Complementary, Gene Expression Regulation, Developmental, Protein Isoforms, Reverse Transcriptase Polymerase Chain Reaction
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