Is Damage and Repair of DNA Required for Differentiation?
DNA 的损伤和修复是分化所必需的吗?
基本信息
- 批准号:63480139
- 负责人:
- 金额:$ 4.16万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for General Scientific Research (B)
- 财政年份:1988
- 资助国家:日本
- 起止时间:1988 至 1990
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
A finding that HL60 cells when exposed to ultraviolet light (UV) underwent terminal differentiation has led to a question that does transient formation of single stranded brakes (SSB) in nuclear DNA as T-T dimers formed by UV are repaired induced the cell differentiation? Hence, we examined the validity of hypothesis that "Formation of SSB in DNA and their repair is required for cell differentiation and aging". A series of experiments were carried out using peripheral lymphocytes. To carry out the experiments, an in situ nick translation method was developed in order to localize SSB histochemically in each cell nuclei. When peripheral lymphocytes were exposed to UV, SSB was formed about 2 hours after the UV irradiation and the SSB gradually decreased thereafter. The T-T dimers were most frequent immediately after the irradiation and gradually decreased. These findings together with the previous finding that when the lymphocytes were exposed to UV, the lymphocytes produced a series of proteins which appear when the cells were stimulated with mitogen suggested that the SSB formation and their repair are associated with the cell differentiation. To examine whether the phenomenon also takes place in in vivo, ears of mice were exposed to UV and studies similar to that done on the lymphocytes were carried out. It was found that the basal cells in epidermis has an ability to repair SSB whereas cells in prickle cell layers has lost the ability. In the basal cells, there were pre-existed SSB and newly formed SSB. The former are inaccessible to DNA polymerase and only the latter were repaired. These finding suggested that in a given nuclei there are two domains, one where SSB are repaired and transcription from DNA to hnRNA takes place and another where SSB remains and no transcription takes place.
HL 60细胞在紫外线照射下发生终末分化的研究结果引发了一个问题,即随着紫外线照射形成的T-T二聚体被修复,核DNA中瞬时形成的单链刹车(single stranded brake,SSB)是否诱导了细胞分化?因此,我们检验了“DNA中SSB的形成及其修复是细胞分化和衰老所必需的”这一假设的有效性。用外周血淋巴细胞进行了一系列实验。为了进行实验,开发了原位切口平移方法,以便在每个细胞核中组织化学地定位SSB。当外周淋巴细胞暴露于紫外线时,紫外线照射后约2小时形成SSB,此后SSB逐渐减少。T-T二聚体在照射后立即出现最多,并逐渐减少。这些发现与以前的发现一起,当淋巴细胞暴露于UV时,淋巴细胞产生一系列蛋白质,这些蛋白质在细胞被有丝分裂原刺激时出现,这表明SSB的形成及其修复与细胞分化有关。为了研究这种现象是否也发生在体内,将小鼠的耳朵暴露在紫外线下,并进行了类似于淋巴细胞的研究。结果发现,表皮中的基底细胞具有修复SSB的能力,而棘细胞层中的细胞已经失去了这种能力。在基底细胞中,既有已存在的SSB,也有新形成的SSB。前者不能被DNA聚合酶修复,只有后者能被修复。这些发现表明,在给定的细胞核中有两个结构域,一个是SSB被修复并发生从DNA到hnRNA的转录的结构域,另一个是SSB保留并不发生转录的结构域。
项目成果
期刊论文数量(122)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
P.K.Nakane: "Proliferating cell nuclear antigene(PCNA/cyclin):Review and some new findings." Acta Histochem.Cytochem.22. 105-116 (1989)
P.K.Nakane:“增殖细胞核抗原(PCNA/细胞周期蛋白):回顾和一些新发现。”
- DOI:
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- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
T.Koji: "Use of nucleotides as an alternative to formamide in nonーradioactive in situ hybridization." Acta Histochem. Cytochem.23. 327-334 (1990)
T. Koji:“在非放射性原位杂交中使用核苷酸作为甲酰胺的替代品。” Acta Histochem.23(1990)。
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中根 一穂: "組織細胞化学 1990" 日本組織細胞化学会, 46-50 (1990)
Kazuho Nakane:“组织细胞化学 1990” 日本组织细胞化学学会,46-50 (1990)
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S. Nozawa: "The mechanism of placental alkalin phosphatase induction in vitro" Cell Biochem. Funct. 7. 227-232 (1989)
S. Nozawa:“胎盘碱性磷酸酶体外诱导机制”Cell Biochem。
- DOI:
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- 影响因子:0
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T. Koji: "Review : Localization in situ of specific mRNA using Thymine-Thymine dimerized DNA probes." Acta Path. Japonica. 40. 793-807 (1990)
T. Koji:“综述:使用胸腺嘧啶-胸腺嘧啶二聚化 DNA 探针对特定 mRNA 进行原位定位。”
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- 影响因子:0
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NAKANE Paul K.其他文献
NAKANE Paul K.的其他文献
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{{ truncateString('NAKANE Paul K.', 18)}}的其他基金
Southwestern histochemical localization of regulatory element binding proteins for rat anterior pituitary hormones.
大鼠垂体前叶激素调节元件结合蛋白的西南组织化学定位。
- 批准号:
06454143 - 财政年份:1994
- 资助金额:
$ 4.16万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
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