Gene-specific DNA repair in terminally differentiating rat myoblasts

Ho, Linus; Hanawalt, Philip C.

doi:10.1016/0921-8777(91)90047-s

Cited by 36 publications

(7 citation statements)

References 39 publications

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“…Within the context of the murine embryo at midgestation, it seems that NER capacity does not necessarily correlate with proliferative potential. This fact is consistent with other studies that found that NER does not correspond to the differentiative status [15].…”

Section: Discussionsupporting

confidence: 93%

“…However, Kaufman et al [14], studying unscheduled DNA synthesis (UDS) after UV irradiation in a rat L8 muscle cell subclone, have disputed these findings, observing instead constant levels of repair throughout differentiation except for a transient period of increased repair immediately following the cessation of replicative DNA synthesis. A study by Ho and Hanawalt [15] attempted to address this question using two different methods of measuring DNA repair in terminally differentiating L8 rat myoblasts: (i) repair replication and (ii) removal of T4 endonuclease V-sensitive sites (ESS). The results of this study concur with those of Kaufman et al [14] in that there were no significant differences detected in ESS removal between exponentially growing myoblasts and that in differentiating myotubes.…”

Section: Introductionmentioning

confidence: 99%

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Elevated DNA Excision Repair Capacity in the Extraembryonic Mesoderm of the Midgestation Mouse Embryo

Latimer

Hultner

Cleaver

et al. 1996

Experimental Cell Research

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In order to determine whether there is differential cell-type-specific DNA repair we measured the nucleotide excision repair capacity of the four distinct cell lineages that comprise the extraembryonic yolk sac using the unscheduled DNA synthesis assay. Yolk sacs from mouse embryos at 11.5-12.5 days gestation were microdissected to yield purified trophoblast, parietal endoderm, mesoderm, and visceral endoderm, as well as fetal skin fibroblasts which were then grown as primary explants. At this midgestational stage of development, the yolk sac provides essential functions for the sustenance of the embryo while the complex process of organogenesis is proceeding in the liver, kidney, and gut. Trophoblast giant cells, parietal endoderm, and visceral endoderm all demonstrated low levels of unscheduled DNA synthesis consistent with levels measured in adult mouse skin fibroblasts. As has previously been documented, embryonic mouse skin fibroblasts were reproducibly 2-to 3-fold higher than adult mouse skin fibroblasts in levels of DNA excision repair. The extraembryonic mesoderm, however, displayed a statistically significant level of unscheduled DNA synthesis 10-fold higher than adult mouse skin fibroblasts or the other lineages of the midgestation yolk sac. Further, the S-indexes of these lineages were also determined to assess the possible relevance of differential repair to the proliferative status of the cells. These data demonstrate that DNA excision repair capacity is lineage-specific during embryogenesis in the mouse. These studies may begin to provide a context for understanding the perplexing developmental aspects such as the characteristic congenital abnormalities associated with the human heritable DNA repair deficiency diseases.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Elevated DNA Excision Repair Capacity in the Extraembryonic Mesoderm of the Midgestation Mouse Embryo

Latimer

Hultner

Cleaver

et al. 1996

Experimental Cell Research

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“…This phenomenon, which we tentatively have termed differentiation-associated repair (DAR), seems to be confined to transcribed genes, as judged by the poor repair of the silent glucagon gene in hNT neurons. Such a situation was previously encountered in two rodent model systems, rat myoblasts differentiating to myocytes (13) and rat PC12 pheochromocytoma cells that display a neuron-like phenotype upon differentiation (reviewed in reference 11). Human HL60 promyelocytic leukemia cells also showed an improved repair of the nontranscribed strand in the c-myc gene after differentiation (14).…”

Section: Discussionmentioning

confidence: 97%

Terminally Differentiated Human Neurons Repair Transcribed Genes but Display Attenuated Global DNA Repair and Modulation of Repair Gene Expression

Nouspikel

Hanawalt

2000

Molecular and Cellular Biology

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Repair of UV-induced DNA lesions in terminally differentiated human hNT neurons was compared to that in their repair-proficient precursor NT2 cells. Global genome repair of (6-4)pyrimidine-pyrimidone photoproducts was significantly slower in hNT neurons than in the precursor cells, and repair of cyclobutane pyrimidine dimers (CPDs) was not detected in the hNT neurons. This deficiency in global genome repair did not appear to be due to denser chromatin structure in hNT neurons. By contrast, CPDs were removed efficiently from both strands of transcribed genes in hNT neurons, with the nontranscribed strand being repaired unexpectedly well. Correlated with these changes in repair during neuronal differentiation were modifications in the expression of several repair genes, in particular an up-regulation of the two structure-specific nucleases XPG and XPF/ERCC1. These results have implications for neuronal dysfunction and aging.

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“…Indeed, studies with other differentiated cell systems have yielded similar results. Among numerous examples, rat skeletal myocytes exhibited a decrease in repair synthesis in the course of differentiation (3,4), whereas TCR was less affected (4). Mouse 3T3 cells displayed attenuated UV-induced repair synthesis after differentiation into adipocytes (5).…”

mentioning

confidence: 99%

Impaired nucleotide excision repair upon macrophage differentiation is corrected by E1 ubiquitin-activating enzyme

Nouspikel

Hanawalt

2006

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

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Global nucleotide excision repair is greatly attenuated in terminally differentiated mammalian cells. We observed this phenomenon in human neurons and in macrophages, noting that the transcriptioncoupled repair pathway remains functional and that there is no significant reduction in levels of excision repair enzymes. We have discovered that ubiquitin-activating enzyme E1 complements the repair deficiency in macrophage extracts, and although there is no reduction in the concentration of E1 upon differentiation, our results indicate a reduction in phosphorylation of E1. In preliminary studies, we have identified the basal transcription factor TFIIH as the potential target for ubiquitination. We suggest that this unusual type of regulation at the level of the E1 enzyme is likely to affect numerous cellular processes and may represent a strategy to coordinate multiple phenotypic changes upon differentiation by using E1 as a ''master switch.'' DNA repair ͉ TFIIH ͉ ubiquitination ͉ monocytes ͉ differentiated N ucleotide excision repair (NER) is the most versatile DNA repair system; it handles a wide variety of lesions, from UV-induced pyrimidine dimers to bulky chemical adducts, to intrastrand DNA cross-links and even bound protein fragments. The early steps in NER can be divided into two subpathways: global genomic repair (GGR) that recognizes and removes lesions throughout the genome, and transcription-coupled repair (TCR) that preferentially repairs the transcribed strand of active genes, most likely by using translocating RNA polymerase as a lesion sensor.The efficiency of NER is known to be affected by cellular differentiation (reviewed in ref. 1). In particular the GGR subpathway is greatly attenuated in human neurons, either primary (1) or derived from NT2 neuroteratoma cells (2), whereas TCR is still active in both cases. In the terminally differentiated cells, however, the nontranscribed strand in active genes is also efficiently repaired, a phenomenon that we have termed differentiation-associated repair (DAR) and which we have reasoned is required to maintain lesion-free templates for TCR.It seems likely that attenuation of NER at the global genome level, and its reliance on TCR and DAR to maintain the essential active genes, is common in terminally differentiated cells. Indeed, studies with other differentiated cell systems have yielded similar results. Among numerous examples, rat skeletal myocytes exhibited a decrease in repair synthesis in the course of differentiation (3, 4), whereas TCR was less affected (4). Mouse 3T3 cells displayed attenuated UV-induced repair synthesis after differentiation into adipocytes (5). The repair of UV-induced lesions was reduced in differentiated keratinocytes, compared with that in cells from the basal layers of human skin (6). Human neuroblastomas repaired benzo[a]pyrene diol-epoxide adducts less rapidly after differentiation (7), and differentiated mouse neuroblastomas exhibited similar deficiencies in the repair of UV-induced lesions (8).What is the mechanism by whic...

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Gene-specific DNA repair in terminally differentiating rat myoblasts

Cited by 36 publications

References 39 publications

Elevated DNA Excision Repair Capacity in the Extraembryonic Mesoderm of the Midgestation Mouse Embryo

Elevated DNA Excision Repair Capacity in the Extraembryonic Mesoderm of the Midgestation Mouse Embryo

Terminally Differentiated Human Neurons Repair Transcribed Genes but Display Attenuated Global DNA Repair and Modulation of Repair Gene Expression

Impaired nucleotide excision repair upon macrophage differentiation is corrected by E1 ubiquitin-activating enzyme

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