Age-dependent alterations of DNA synthesis. Terminal deoxynucleotidyl transferase and DNA polymerase activities in bone marrow subpopulations from mice

Müller, Wernér E.G.; Ζahn, Rudolf K.; Geurtsen, Werner; Munsch, Nicole

doi:10.1016/0047-6374(80)90055-x

Cited by 8 publications

(2 citation statements)

References 19 publications

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“…DNA polymerase alpha has been found to decline with age in several systems. Declines that have been noted were 2-fold in mouse bone marrow cells (Muller et al, 1980), 2.5-fold in quail oviduct (Muller and Zahn, 19791, and 3-fold and 25-fold in regenerating liver of mice between ages 7 months and 28 months, and 7 months and 32 months, respectively (Fry et al, 1984). These results are in contrast to the unaltered levels of polymerase alpha in aging mouse fibroblasts (Weisman-Shomer et al, 1979).…”

Section: Discussioncontrasting

confidence: 76%

Reduction of DNA synthesis in aging but still proliferating cells

Collins

Chu

1985

Journal Cellular Physiology

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It is well known that cell proliferation (and hence, DNA synthesis) declines in human diploid fibroblast-like cells with increasing passage number. It is not clear whether D N A synthesis declines in t h e remaining cells that are still actively proliferating. Estimations of cell kinetic parameters permitted extrapolations to be made that reflected the declining numbers of cells still capable of D N A replication. D N A synthesis declined with culture age in intact cells, permeabilized cells, and in the isolated nuclear matrix even when corrected for declining numbers of proliferating cells. With age, DNA polymerase alpha and beta activity in cell lysates declined, but when corrected for the remaining proliferating cells, only polymerase alpha activity declined; D N A polymerase alpha and beta activity bound to the nuclear matrix declined, but when corrected for declining proliferation, no decline was apparent for either enzyme. There was an increase in the number of S1-nuclease sensitive sites and breaks in the parental DNA of the dividing cells in older cultures. It is suggested that in aging cultures, not only does overall DNA synthesis decline owing to decreasing cell proliferation, but also that D N A synthesis declines in t h e remaining proliferating cells, that this decline is not due to decreasing amounts of D N A polymerase bound to the nuclear matrix, and that alterations in D N A structure occur.

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Section: Discussioncontrasting

confidence: 76%

Reduction of DNA synthesis in aging but still proliferating cells

Collins

Chu

1985

Journal Cellular Physiology

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“…DNA polymerase a is the major enzyme responsible for the addition of nucleoside monophosphates to the 3'OH ends of RNA primers or growing chains (Fry and Loeb, 1986). Total cellular activities of DNA polymerase 01 were observed to decline in aging animals (Muller and Zahn, 1979;Muller et al, 1980;Fry et al, 1984) and in aging cell cultures (Murray, 1981;Krauss and Linn, 1982;Pendergrass et al, 1982;Busbee et al, 1987). However, in these studies, the declining num-bers of proliferating cells were not determined, hence appropriate corrections cannot be made.…”

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confidence: 99%

Reduction of DNA primase activity in aging but still proliferating cells

Collins

Chu

1990

Journal Cellular Physiology

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The basis of the well-known decline in cell proliferation with increasing passage number of human diploid fibroblast-like cell cultures is not known. It has been found that DNA synthesis was deficient in the remaining but still proliferating cells, but when appropriate corrections reflecting the remaining dividing cells were made, the amount of DNA polymerase alpha bound to nuclear matrices was normal [Collins and Chu: Journal of Cellular Physiology 124:165-173, 1985]. In the present study, the declining percentages of S-phase and dividing cells were determined to provide better estimates of functional culture age than passage number. The amounts of DNA polymerase alpha and DNA primase activity were determined in cell lysates, permeabilized cells, and bound to nucleoids, which are residual nuclear structures similar to nuclear matrices except that no DNase-digestion step is employed. As expected, IMR 90 DNA synthesis declined with age, even after corrections for the declining numbers of proliferating cells. DNA polymerase alpha and DNA primase activity in cell lysates, permeabilized cells, and bound to nucleoids declined with increasing age. However, after appropriate corrections for the declining fraction of proliferating cells, the only activity that declined was that of DNA primase bound to nucleoids. Thus, a decrease in the binding of DNA primase to the nuclear site of DNA synthesis may account for the decreased DNA synthesis in aging but still proliferating cells.

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Ontogeny of Terminal Deoxynucleotidyl Transferase Containing Lymphocytes in Rats and Mice

Goldschneider

1982

Advances in Experimental Medicine and Biology

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Age-dependent alterations of DNA synthesis. Terminal deoxynucleotidyl transferase and DNA polymerase activities in bone marrow subpopulations from mice

Cited by 8 publications

References 19 publications

Reduction of DNA synthesis in aging but still proliferating cells

Reduction of DNA synthesis in aging but still proliferating cells

Reduction of DNA primase activity in aging but still proliferating cells

Ontogeny of Terminal Deoxynucleotidyl Transferase Containing Lymphocytes in Rats and Mice

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