Related Experiment Videos
Mechanisms of induction of apoptotic DNA fragmentation
N N Khodarev1, I A Sokolova, A T Vaughan
1Department of Radiotherapy, Loyola University Medical Center, Maywood, IL 60153, USA.
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.
Insights
Mechanisms of DNA fragmentation in apoptotic cells are explored. This review details pathways involving nucleases and chromatin structure, crucial for understanding cell death indicators.
Area of Science:
- Cell Biology
- Molecular Biology
- Radiation Biology
Background:
- Apoptotic DNA fragmentation involves cleavage of large DNA fragments (0.4-1.0 Mbp, 50 kbp) and internucleosomal DNA laddering.
- While initial cleavage is common in apoptosis, DNA laddering is not always observed.
- Endonucleases mediating chromatin cleavage are classified by substrate, cleavage mode, and cofactor needs.
Purpose of the Study:
- To elucidate mechanisms controlling apoptotic DNA fragmentation in irradiated cells.
- To review pathways of chromatin fragmentation.
- To examine the roles of nucleases and chromatin structure in this process.
Main Methods:
- Literature review of existing research on apoptotic DNA fragmentation.
- Analysis of endonuclease classifications and functions.
- Discussion of chromatin structure alterations.
Main Results:
- Apoptotic DNA fragmentation is a complex process involving multiple cleavage events.
- Endonucleases play a critical role, with varying classification criteria.
- Chromatin structure is a significant factor influencing fragmentation.
Conclusions:
- Three primary pathways of DNA fragmentation are proposed: endonuclease upregulation, redistribution, and chromatin structure changes.
- Understanding these pathways is key to interpreting DNA fragmentation as an apoptosis indicator.
- Further research is needed to fully delineate the interplay between nucleases and chromatin structure.