Changes in DNA polymerases .alpha., .beta., and .gamma. during the replicative life span of cultured human fibroblasts

Biochemistry ◽  
1982 ◽  
Vol 21 (5) ◽  
pp. 1002-1009 ◽  
Author(s):  
Sharon Wald Krauss ◽  
Stuart Linn
Keyword(s):  
Life Span ◽  
Human Fibroblasts ◽  
Dna Polymerases ◽  
Replicative Life Span ◽  
Cultured Human Fibroblasts ◽  
Alpha Beta

scholarly journals Control of Replicative Life Span in Human Cells: Barriers to Clonal Expansion Intermediate Between M1 Senescence and M2 Crisis

1999 ◽  
Vol 19 (4) ◽  
pp. 3103-3114 ◽  
Author(s):  
J. A. Bond ◽  
M. F. Haughton ◽  
J. M. Rowson ◽  
P. J. Smith ◽  
V. Gire ◽  
...  
Keyword(s):  
Life Span ◽  
Clonal Evolution ◽  
Human Fibroblasts ◽  
Fold Increase ◽  
Clonal Expansion ◽  
Suppressor Gene ◽  
Human Cells ◽  
Cell Type ◽  
Replicative Life Span ◽  
Population Doublings

ABSTRACT The accumulation of genetic abnormalities in a developing tumor is driven, at least in part, by the need to overcome inherent restraints on the replicative life span of human cells, two of which—senescence (M1) and crisis (M2)—have been well characterized. Here we describe additional barriers to clonal expansion (Mint) intermediate between M1 and M2, revealed by abrogation of tumor-suppressor gene (TSG) pathways by individual human papillomavirus type 16 (HPV16) proteins. In human fibroblasts, abrogation of p53 function by HPVE6 allowed escape from M1, followed up to 20 population doublings (PD) later by a second viable proliferation arrest state, MintE6, closely resembling M1. This occurred despite abrogation of p21WAF1 induction but was associated with and potentially mediated by a further ∼3-fold increase in p16INK4a expression compared to its level at M1. Expression of HPVE7, which targets pRb (and p21WAF1), also permitted clonal expansion, but this was limited predominantly by increasing cell death, resulting in a MintE7 phenotype similar to M2 but occurring after fewer PD. This was associated with, and at least partly due to, an increase in nuclear p53 content and activity, not seen in younger cells expressing E7. In a different cell type, thyroid epithelium, E7 also allowed clonal expansion terminating in a similar state to MintE7 in fibroblasts. In contrast, however, there was no evidence for a p53-regulated pathway; E6 was without effect, and the increases in p21WAF1 expression at M1 and MintE7 were p53 independent. These data provide a model for clonal evolution by successive TSG inactivation and suggest that cell type diversity in life span regulation may determine the pattern of gene mutation in the corresponding tumors.

scholarly journals Control of the Replicative Life Span of Human Fibroblasts by p16 and the Polycomb Protein Bmi-1

2003 ◽  
Vol 23 (1) ◽  
pp. 389-401 ◽  
Author(s):  
Koji Itahana ◽  
Ying Zou ◽  
Yoko Itahana ◽  
Jose-Luis Martinez ◽  
Christian Beausejour ◽  
...  
Keyword(s):  
Life Span ◽  
Replicative Senescence ◽  
Human Fibroblasts ◽  
Ring Finger ◽  
Dominant Negative ◽  
Life Span Extension ◽  
Replicative Life Span ◽  
Polycomb Protein ◽  
Human Fibroblast Strains ◽  
Dominant Negative Activity

ABSTRACT The polycomb protein Bmi-1 represses the INK4a locus, which encodes the tumor suppressors p16 and p14ARF. Here we report that Bmi-1 is downregulated when WI-38 human fibroblasts undergo replicative senescence, but not quiescence, and extends replicative life span when overexpressed. Life span extension by Bmi-1 required the pRb, but not p53, tumor suppressor protein. Deletion analysis showed that the RING finger and helix-turn-helix domains of Bmi-1 were required for life span extension and suppression of p16. Furthermore, a RING finger deletion mutant exhibited dominant negative activity, inducing p16 and premature senescence. Interestingly, presenescent cultures of some, but not all, human fibroblasts contained growth-arrested cells expressing high levels of p16 and apparently arrested by a p53- and telomere-independent mechanism. Bmi-1 selectively extended the life span of these cultures. Low O2 concentrations had no effect on p16 levels or life span extension by Bmi-1 but reduced expression of the p53 target, p21. We propose that some human fibroblast strains are more sensitive to stress-induced senescence and have both p16-dependent and p53/telomere-dependent pathways of senescence. Our data suggest that Bmi-1 extends the replicative life span of human fibroblasts by suppressing the p16-dependent senescence pathway.

scholarly journals Influence of chlorate on proteoglycan biosynthesis by cultured human fibroblasts.

1988 ◽  
Vol 263 (26) ◽  
pp. 12886-12892 ◽  
Author(s):  
H Greve ◽  
Z Cully ◽  
P Blumberg ◽  
H Kresse
Keyword(s):  
Human Fibroblasts ◽  
Cultured Human Fibroblasts

scholarly journals Fatty alcohol metabolism in cultured human fibroblasts. Evidence for a fatty alcohol cycle.

1987 ◽  
Vol 262 (36) ◽  
pp. 17412-17419 ◽  
Author(s):  
W B Rizzo ◽  
D A Craft ◽  
A L Dammann ◽  
M W Phillips
Keyword(s):  
Fatty Alcohol ◽  
Human Fibroblasts ◽  
Alcohol Metabolism ◽  
Cultured Human Fibroblasts

L-iduronidase in cultured human fibroblasts and liver

1971 ◽  
Vol 42 (2) ◽  
pp. 340-345 ◽  
Author(s):  
Reuben Matalon ◽  
J.A. Cifonelli ◽  
Albert Dorfman
Keyword(s):  
Human Fibroblasts ◽  
Cultured Human Fibroblasts

scholarly journals The transport of neutral amino acids in cultured human fibroblasts.

1980 ◽  
Vol 255 (3) ◽  
pp. 929-936 ◽  
Author(s):  
G.C. Gazzola ◽  
V. Dall'Asta ◽  
G.G. Guidotti
Keyword(s):  
Amino Acids ◽  
Human Fibroblasts ◽  
Neutral Amino Acids ◽  
Cultured Human Fibroblasts
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