Mechanisms of induction of apoptotic DNA fragmentation.
OBJECTIVE
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.


BACKGROUND
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.
Khodarev
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NN
Department of Radiotherapy, Loyola University Medical Center, Maywood, IL 60153, USA.
Sokolova
I A
IA
Vaughan
A T
AT
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism; D006801:Humans
D002843:Chromatin; D004247:DNA; D004720:Endonucleases