CHROMATIN STRUCTURE AND DNA DAMAGE-INDUCED GENE EXPRESSION (MEETING ABSTRACT)

Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

CHROMATIN STRUCTURE AND DNA DAMAGE-INDUCED GENE EXPRESSION (MEETING ABSTRACT)

Environmental Carcinogenesis and Its Prevention: The Head and Neck Cancer Model. October 6-8, 1991, Hershey, PA, Organ Systems Coordinating Branch of the National Cancer Institute and The University of Texas M. D. Anderson Cancer Center, p. 9, 1991.. Unique Identifier : AIDSLINE ICDB/92682212
Valerie K; Massey Cancer Center, Medical Coll. of Virginia, Virginia; Commonwealth Univ., Richmond, VA

Abstract: Chromatin structure modulates vital cellular processes such as DNA replication, repair and transcription. Recent studies suggest that after DNA damage, these three systems overlap to a certain extent and may share common functional elements. Most likely, chromatin structure plays an important regulatory role. In order to study DNA damage-induced gene expression, we are using human cells stably transfected with the bacterial cat gene under control of the HIV-1 regulatory region. This system has allowed us to partly dissect DNA damage-induced HIV-1 gene expression at a mechanistic level. We find that agents which introduce bulky DNA damage (W-mimetic), but not base damage (x-ray mimetic), activate early HIV-1 gene expression in a transcription-dependent and protein synthesis-independent fashion. On the other hand, gamma-rays appear to increase HIV-1 gene expression more slowly and less pronounced than UV, and cannot be observed until after several days. UV, but not gamma-rays, result in chromatin decondensation. Drugs which interfere with phosphorylation and poly-ADP ribosylation inhibit the UV effect. Our results suggest a major role of chromatin structure in modulating HIV-1 gene expression after DNA damage, which correlates well with type of DNA repair (nucleotide vs base excision) involved.

Keywords: Adenosine Diphosphate Ribose/METABOLISM Cell Line Chloramphenicol Acetyltransferase/GENETICS *Chromatin *DNA Damage *Gene Expression/RADIATION EFFECTS Genes, Viral Human HIV-1/GENETICS Phosphorylation Regulatory Sequences, Nucleic Acid Transfection Ultraviolet Rays ABSTRACT
920730
M9271110

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