Overexpression of Helicard, a CARD-containing helicase cleaved during apoptosis, accelerates DNA degradation.

Details

Serval ID
serval:BIB_CE1131445D35
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Overexpression of Helicard, a CARD-containing helicase cleaved during apoptosis, accelerates DNA degradation.
Journal
Current Biology
Author(s)
Kovacsovics M., Martinon F., Micheau O., Bodmer J.L., Hofmann K., Tschopp J.
ISSN
0960-9822 (Print)
ISSN-L
0960-9822
Publication state
Published
Issued date
2002
Volume
12
Number
10
Pages
838-843
Language
english
Abstract
Apoptotic cell death is characterized by several morphological nuclear changes, such as chromatin condensation and extensive fragmentation of chromosomal DNA. These alterations are primarily triggered through the activation of caspases, which subsequently cleave nuclear substrates. Caspase-3 induces processing of Acinus, which leads to chromatin condensation. DNA fragmentation is dependent on the DNase CAD, which is released from its inhibitor, ICAD, upon cleavage by caspase-3. DNA degradation is also induced by AIF and endonuclease G, which are both released from mitochondria upon death stimuli but do not require prior processing by caspases for their DNase activity. Here we report the identification of a widely expressed helicase designated Helicard, which contains two N-terminal CARD domains and a C-terminal helicase domain. Upon apoptotic stimuli, Helicard is cleaved by caspases, thereby separating the CARD domains from the helicase domain. While Helicard localizes in the cytoplasm, the helicase-containing fragment is found in the nucleus. Helicard accelerates Fas ligand-mediated DNA degradation, whereas a noncleavable or a helicase-dead Helicard mutant does not, implicating Helicard in the nuclear remodeling occurring during apoptosis.
Keywords
Amino Acid Sequence, Animals, Apoptosis, Caspase 3, Caspases/metabolism, DNA Fragmentation, DNA Helicases/chemistry, DNA Helicases/genetics, Gene Expression Profiling, Hela Cells, Humans, Mice, Molecular Sequence Data, Organ Specificity, Polymerase Chain Reaction, Protein Structure, Tertiary, Rats, Sequence Homology, Amino Acid, Transfection
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:19
Last modification date
20/08/2019 15:48
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