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Overreplication and recombination of DNA in higher eukaryotes: potential consequences and biological implications

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TLDR
In this paper, the authors propose a model that accounts for the generation of a wide variety of chromosomal aberrations-rearrangements, resulting from the various ways in which the overreplicated strands can undergo recombination.
Abstract
We propose that a fundamental problem in the faithful replication of complex chromosomes of higher eukaryotes is the proper control of both the number and timing of the multiple initiations of replication on single chromosomes. When replication patterns are disrupted by any of a variety of agents, overreplication of DNA can occur. We propose a model that accounts for the generation of a wide variety of chromosomal aberrations-rearrangements, resulting from the various ways in which the overreplicated strands can undergo recombination. We also discuss certain implications of the generation of chromosomal alterations in higher eukaryotes as they may relate to cancer chemotherapy, cancer progression, aging, and rapid speciation-evolution.

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Journal ArticleDOI

Replicative senescence: the human fibroblast comes of age

TL;DR: Identification of participating genes and clarification of their mechanisms of action will help to elucidate the universal cellular decline of biological aging and an important obverse manifestation, the rare escape of cells from senescence leading to immortalization and oncogenesis.
Journal Article

Tumor cell instability, diversification, and progression to the metastatic phenotype: from oncogene to oncofetal expression

Garth L. Nicolson
- 15 Mar 1987 - 
TL;DR: It is proposed that tumor cell instability and the expression of cellular diversification mechanisms ensure that malignant neoplasms contain heterogeneous, phenotypically diverse tumor cell subpopulations.
Journal ArticleDOI

Gene amplification in cancer

TL;DR: Clinically, amplification has prognostic and diagnostic usefulness, and is a mechanism of acquired drug resistance in patients with tumors and associated with overexpression of the amplified gene(s).
Journal ArticleDOI

Camptothecin: current perspectives.

TL;DR: This review summarizes the current status of studies of the mechanism of action of camptothecin, including topoisomerase I inhibition and additional cellular responses, and a systematic evaluation of novel and important analogues of camPTothecin and their contribution to the current structure-activity profile are considered.
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