The immortal strand hypothesis: still non-randomly segregating opinions

Wakeman, Jane A.; Hmadcha, Abdelkrim; Soria, Bernat; McFarlane, Ramsay J.

doi:10.1515/bmc-2011-0053

Cited by 3 publications

(3 citation statements)

References 57 publications

(47 reference statements)

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“…Coined as “immortal” strand retention, it was originally proposed as a strategy to maintain DNA purity in stem cells while the copied strands, potentially carrying mutations from replication, were segregated to nonstem cell progeny ( 22 ). Whether this strategy is actually utilized by stem cells remains controversial ( 23 – 25 ). Immortal strand segregation has been tested in Caulobacter crescentus ( 26 , 27 ) and Bacillus subtilis ( 28 ); however, none of these studies showed any segregational strand preference between daughter cells.…”

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confidence: 99%

Nonrandom segregation of sister chromosomes by Escherichia coli MukBEF

Mäkelä

Uphoff

Sherratt

2021

Proc. Natl. Acad. Sci. U.S.A.

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Structural maintenance of chromosomes (SMC) complexes contribute to chromosome organization in all domains of life. In Escherichia coli, MukBEF, the functional SMC homolog, promotes spatiotemporal chromosome organization and faithful chromosome segregation. Here, we address the relative contributions of MukBEF and the replication terminus (ter) binding protein, MatP, to chromosome organization–segregation. We show that MukBEF, but not MatP, is required for the normal localization of the origin of replication to midcell and for the establishment of translational symmetry between newly replicated sister chromosomes. Overall, chromosome orientation is normally maintained through division from one generation to the next. Analysis of loci flanking the replication termination region (ter), which demark the ends of the linearly organized portion of the nucleoid, demonstrates that MatP is required for maintenance of chromosome orientation. We show that DNA-bound β2-processivity clamps, which mark the lagging strands at DNA replication forks, localize to the cell center, independent of replisome location but dependent on MukBEF action, and consistent with translational symmetry of sister chromosomes. Finally, we directly show that the older (“immortal”) template DNA strand, propagated from previous generations, is preferentially inherited by the cell forming at the old pole, dependent on MukBEF and MatP. The work further implicates MukBEF and MatP as central players in chromosome organization, segregation, and nonrandom inheritance of genetic material and suggests a general framework for understanding how chromosome conformation and dynamics shape subcellular organization.

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confidence: 99%

Nonrandom segregation of sister chromosomes by Escherichia coli MukBEF

Mäkelä

Uphoff

Sherratt

2021

Proc. Natl. Acad. Sci. U.S.A.

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“…'Immortal' strand retention was originally proposed as a strategy to maintain DNA purity in stem cells while the copied strands, potentially carrying mutations from replication, were segregated to non-stem cell progeny (Cairns, 1975). Whether this strategy is actually utilized by stem cells remains controversial (Lansdorp, 2007;Rando, 2007;Wakeman et al, 2012). Ancestral strand segregation has also been tested in C. crescentus (Marczynski et al, 1990;Osley and Newton, 1974) and B.…”

Section: Introductionmentioning

confidence: 99%

Non-random segregation of sister chromosomes byEscherichia coliMukBEF axial cores

Mäkelä

Uphoff

Sherratt

2020

Preprint

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SummaryThe Escherichia coli structural maintenance of chromosomes complex, MukBEF, forms axial cores to chromosomes that determine their spatio-temporal organization. Here, we show that axial cores direct chromosome arms to opposite poles and generate the translational symmetry between newly replicated sister chromosomes. MatP, a replication terminus (ter) binding protein, prevents chromosome rotation in the longitudinal cell axis by displacing MukBEF from ter, thereby maintaining the linear shape of axial cores. During DNA replication, MukBEF-MatP action directs lagging strands towards the cell center, marked by accumulation of DNA-bound β2-clamps in the wake of the replisome, in a process necessary for translational symmetry. Finally, the ancestral template DNA strand, propagated from previous generations, is preferentially inherited by the cell forming at the old pole, dependent on MukBEF-MatP. The work demonstrates how chromosome organization-segregation fosters non-random inheritance of genetic material and provides a framework for understanding how chromosome conformation and dynamics shape subcellular organization.HighlightsLinear MukBEF axial cores are required for left-oriC-right chromosome organizationMatP prevents longitudinal nucleoid rotation by linearizing the axial coresMukBEF axial cores direct lagging strands towards the cell centerThe ancestral DNA strand is preferentially segregated to the older pole cell

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“…The basic assumption of the immortal strand hypothesis is that, in tissues with high cellular turnover, a subpopulation of stem cells avoids accumulating mutations arising from errors in DNA replication by systematically inheriting, for each chromosome, the chromatid with the older template strand (Cairns 1975). Accumulating evidence from studies of stem cells in various tissues has confirmed that nonrandom chromosome segregation could take place in neural (Karpowicz et al 2005) and muscle stem cells (Rocheteau et al 2012;Shinin et al 2006) (reviewed in (Wakeman et al 2012)).…”

Section: Introductionmentioning

confidence: 99%

Random chromosome segregation in mouse intestinal epithelial stem cells

Legraverend

Jay

2013

Chromosome Res

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The mammalian intestinal epithelium is endowed with a high cell turnover sustained by a few stem cells located in the bottoms of millions of crypts. Until recently, it was generally assumed that the extreme sensitivity to DNA damaging agents leading to cell death and the asymmetric mode of chromosome segregation of intestinal epithelial stem cells prevented the illicit survival of mutated stem cells and guarded against mistakes leading to aneuploidy and neoplastic transformation. Recent evidence points instead to a pool of mutipotent self-renewing stem cells capable of repairing DNA by homologous recombination significantly more efficiently than other crypt cells. Furthermore, the equilibrium between cell division and differentiation is achieved at the level of the cell population obeying to a random mode of chromosome segregation and a predominantly symmetric mode of cell division. This review summarizes the experimental findings on the mode of cell division adopted by intestinal epithelial stem cells.

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The immortal strand hypothesis: still non-randomly segregating opinions

Cited by 3 publications

References 57 publications

Nonrandom segregation of sister chromosomes by Escherichia coli MukBEF

Nonrandom segregation of sister chromosomes by Escherichia coli MukBEF

Non-random segregation of sister chromosomes byEscherichia coliMukBEF axial cores

Random chromosome segregation in mouse intestinal epithelial stem cells

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