Review Mechanisms of induction of apoptotic DNA fragmentation

Purpose: Despite its common use as an indicator of apoptosis, little is known about the mechanisms controlling apoptotic DNA fragmentation in irradiated cells. This review discusses the pathways of chromatin fragmentation, and the role of both nucleases and chromatin structure in this process. Defin...

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Bibliographic Details
Published in:International journal of radiation biology Vol. 73; no. 5; pp. 455 - 467
Main Author: N. KHODAREV I. A. SOKOLOVA A. T. M. VAUGHAN, N.
Format: Journal Article
Language:English
Published: Informa UK Ltd 1998
Taylor & Francis
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Summary:Purpose: Despite its common use as an indicator of apoptosis, little is known about the mechanisms controlling apoptotic DNA fragmentation in irradiated cells. This review discusses the pathways of chromatin fragmentation, and the role of both nucleases and chromatin structure in this process. Definitions: DNA fragmentation linked to apoptosis is a combination of cleavage events excising both large DNA fragments within the range 0.4-1.0 Mbp and 50 kbp followed by random cuts within internucleosomal regions (i.e. DNA laddering) . The first two cleavage steps can be detected in virtually all apoptotic cells, but DNA laddering is not ubiquitously observed. Endonucleases that mediate this cleavage of chromatin may be classified by substrate specificity, mode of DNA cleavage and their cofactor requirements. Conclusions: Three major pathways of DNA fragmentation are proposed and discussed: (1) upregulation of endonucleases, (2) their intranuclear/intracellular redistribution and (3) primary changes of chromatin structure.
ISSN:0955-3002
1362-3095
DOI:10.1080/095530098141997