This paper develops the semiconservative quasispecies equations for genomes consisting of an arbitrary number of chromosomes. We assume that the chromosomes are distinguishable, so that we are effectively considering haploid genomes. We derive the quasispecies equations under the assumption of arbitrary lesion repair efficiency, and consider the cases of both random and immortal strand chromosome segregation. We solve the model in the limit of infinite sequence length for the case of the static single fitness peak landscape, where the master genome has a first-order growth rate constant of k>1, and all other genomes have a first-order growth rate constant of 1. If we assume that each chromosome can tolerate an arbitrary number of lesions, so that only one master copy of the strands is necessary for a functional chromosome, then for random chromosome segregation we obtain an equilibrium mean fitness of [equation in text] below the error catastrophe, while for immortal strand co-segregation we obtain kappa (t=infinity)=k[e(-mu(1-lambda/2))+e(-mulambda/2)-1] (N denotes the number of chromosomes, lambda denotes the lesion repair efficiency, and mu is identical with epsilonL, where epsilon is the per base-pair mismatch probability, and L is the total genome length). It follows that immortal strand co-segregation leads to significantly better preservation of the master genome than random segregation when lesion repair is imperfect. Based on this result, we conjecture that certain classes of tumor cells exhibit immortal strand co-segregation.
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http://dx.doi.org/10.1016/j.jtbi.2006.01.016 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Département de Biologie, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.
To achieve replicative immortality, cancer cells must activate telomere maintenance mechanisms. In 10 to 15% of cancers, this is enabled by recombination-based alternative lengthening of telomeres pathways (ALT). ALT cells display several hallmarks including heterogeneous telomere length, extrachromosomal telomeric repeats, and ALT-associated PML bodies.
View Article and Find Full Text PDFBioorg Med Chem Lett
December 2024
Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, HarBin Medical University, Harbin, PR China. Electronic address:
The telomeric G-quadruplex (G4) along with the telomerase catalytic subunit hTERT are crucial in the extension of telomeres. Tumor cells can establish replicative immortality by activating the telomere-maintenance mechanism (TMM).Small molecule ligands can limit cancer telomere lengthening by by targeting at G4 and hTERT.
View Article and Find Full Text PDFPLoS One
December 2024
Department of Biological Sciences, University of South Carolina, Columbia, South Carolina, United States of America.
Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic condition characterized by features of accelerated aging, and individuals with HGPS seldom live beyond their mid-teens. The syndrome is commonly caused by a point mutation in the LMNA gene which codes for lamin A and its splice variant lamin C, components of the nuclear lamina. The mutation causing HGPS leads to production of a truncated, farnesylated form of lamin A referred to as "progerin.
View Article and Find Full Text PDFbioRxiv
November 2024
Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, 99163, USA.
Multiple viruses that are highly pathogenic in humans are known to have evolved in bats. How bats tolerate infection with these viruses, however, is poorly understood. As viruses engage in a wide range of interactions with their hosts, it is essential to study bat viruses in a system that resembles their natural environment like bat-derived cellular models.
View Article and Find Full Text PDFRadiat Prot Dosimetry
November 2024
Laboratory of Radiological Disasters and Medical Science, International Research Institute of Disaster Science, Tohoku University, 519-1176 Aramaki-aza-Aoba, Aoba-ku, Sendai 980-0845, Japan.
This study investigated the induction of DNA double-strand breaks (DSBs) in the hTERT-immortalized normal human diploid epithelial cells (RPE1-hTERT) continuously exposed to 6000 Bq/ml of tritiated water (HTO) and organically bound tritium (OBT). The relationship of the DSBs induction with the intracellular amount as well as the localization of tritium was also examined. Tritium-labeled thymidine (3H-Thy) and palmitic acid (3H-PA) were used as OBT.
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