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Abortive apoptosis as an initiator of chromosomal translocations
N N Khodarev1, I A Sokolova, A T Vaughan
1Department of Radiotherapy, Loyola University Medical Center, Maywood, IL 60153, USA. nkhodar@luc.edu
Abstract:
Apoptosis is a well-recognized regulator of a cell populations size and structure. Irreversible stages of apoptosis lead to activation of different enzymatic cascades, changes in cell morphology and DNA fragmentation. However, little is known about nuclear events which accompany the initial stages of apoptosis. These events are connected with introduction of limited amounts of double strand breaks into genomic DNA, some of which may be subsequently rejoined. We hypothesize here that the initial stages of apoptotic DNA fragmentation may be reversible and connected with the initiation of recombinational events and certain chromosomal translocations. The factors influencing apoptosis reversibility and cell survival after delivery of apoptotic stimuli may provide new insights into mechanisms of lymphocyte development and tumorigenesis.
Insights
Early apoptosis may involve reversible DNA fragmentation, potentially initiating recombination and chromosomal translocations. Understanding these initial events could illuminate lymphocyte development and cancer mechanisms.
Area of Science:
- Cell biology
- Molecular genetics
- Cancer research
Background:
- Apoptosis regulates cell population size and structure.
- Late-stage apoptosis involves irreversible enzymatic cascades, morphological changes, and DNA fragmentation.
- Nuclear events during early apoptosis remain poorly understood.
Purpose of the Study:
- To investigate nuclear events during the initial stages of apoptosis.
- To hypothesize that early apoptotic DNA fragmentation is reversible.
- To explore the potential link between early apoptosis, recombination, and chromosomal translocations.
Main Methods:
- Analysis of nuclear events during initial apoptosis.
- Investigating DNA double-strand breaks and their repair.
- Exploring potential recombinational events and chromosomal translocations.
Main Results:
- Initial apoptotic DNA fragmentation may involve limited, potentially rejoining double-strand breaks.
- Hypothesized reversibility of early apoptotic DNA fragmentation.
- Potential initiation of recombinational events and chromosomal translocations.
Conclusions:
- Early apoptotic DNA fragmentation might be a reversible process.
- Reversibility is linked to recombination and chromosomal translocations.
- Studying apoptosis reversibility offers insights into lymphocyte development and tumorigenesis.