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哺乳动物精子染色质作为 DNA 降解和 DNA 复制中染色质功能的模型。

Mammalian sperm chromatin as a model for chromatin function in DNA degradation and DNA replication.

机构信息

Institute for Biogenesis Research, John A Burns School of Medicine, University of Hawaii at Manoa, HI 96822, USA.

出版信息

Syst Biol Reprod Med. 2011 Feb;57(1-2):43-9. doi: 10.3109/19396368.2010.505679. Epub 2011 Jan 5.

DOI:10.3109/19396368.2010.505679
PMID:21204750
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3040494/
Abstract

Reproductive biology is considered a specialty field, however, an argument can be made that it is instead generally applicable to many fields of biology. The one-cell embryo is presented here as a model system for the study of eukaryotic DNA replication, apoptotic DNA degradation, and signaling mechanisms between the cytoplasm and nucleus. Two unique aspects of this system combine to make it particularly useful for the study of chromatin function. First, the evolutionary pressure that lead to the extreme condensation of mammalian sperm DNA resulted in a cell with virtually inert chromatin, no DNA replication or transcription ongoing in the sperm cell, and all of the cells in a G(0) state. This chromatin is suddenly transformed into actively transcribing and replicating DNA upon fertilization. Therefore, the sperm chromatin is poised to become active but does not yet possess sufficient components present in somatic chromatin structure for all these processes. The second unique aspect of this system is that the one cell embryo houses two distinct nuclei, termed pronuclei, through the first round of DNA synthesis. This means the sperm cell can be experimentally manipulated to test the affects of the various treatments on the biological functions of interest. Experimental manipulations of the system have already revealed a certain level of plasticity in the coordination of both the timing of DNA synthesis in the two pronuclei and in the response to cellular signals by each pronucleus involved with the progression through the G1/S checkpoint, including the degradation of DNA in the paternal pronucleus. The fact that two nuclei in the same cytoplasm can undergo different responses infers a level of autonomy in the nuclear control of the cell cycle. Thus, the features of mammalian fertilization can provide unique insights for the normal biology of the cell cycle in somatic cells.

摘要

生殖生物学被认为是一个专业领域,但也有人认为它实际上适用于许多生物学领域。本文以单细胞胚胎为模型系统,研究真核生物 DNA 复制、凋亡 DNA 降解以及细胞质和细胞核之间的信号转导机制。这个系统有两个独特的方面,使其特别适合研究染色质功能。首先,导致哺乳动物精子 DNA 极度浓缩的进化压力导致精子细胞的染色质几乎没有活性,精子细胞中没有 DNA 复制或转录,并且所有细胞都处于 G0 状态。这种染色质在受精后突然转变为活跃转录和复制的 DNA。因此,精子染色质准备好变得活跃,但还没有获得体细胞染色质结构中存在的所有这些过程所需的足够成分。该系统的第二个独特方面是,在第一轮 DNA 合成过程中,单细胞胚胎中存在两个不同的核,称为原核。这意味着可以对精子细胞进行实验操作,以测试各种处理对感兴趣的生物学功能的影响。该系统的实验操作已经揭示出,在两个原核中 DNA 合成的时间以及每个原核对 G1/S 检查点的细胞信号的反应的协调方面存在一定程度的可塑性,包括父原核中 DNA 的降解。同一细胞质中的两个核可以做出不同反应这一事实暗示了细胞核对细胞周期的控制具有一定程度的自主性。因此,哺乳动物受精的特征可以为体细胞细胞周期的正常生物学提供独特的见解。

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1
Mammalian sperm chromatin as a model for chromatin function in DNA degradation and DNA replication.哺乳动物精子染色质作为 DNA 降解和 DNA 复制中染色质功能的模型。
Syst Biol Reprod Med. 2011 Feb;57(1-2):43-9. doi: 10.3109/19396368.2010.505679. Epub 2011 Jan 5.
2
Asynchronous DNA replication and origin licensing in the mouse one-cell embryo.小鼠单细胞胚胎中的异步DNA复制与复制起点许可
J Cell Biochem. 2009 May 15;107(2):214-23. doi: 10.1002/jcb.22117.
3
Differential H4 acetylation of paternal and maternal chromatin precedes DNA replication and differential transcriptional activity in pronuclei of 1-cell mouse embryos.在单细胞小鼠胚胎原核中,父本和母本染色质的组蛋白H4乙酰化差异先于DNA复制和转录活性差异出现。
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The ability to organize sperm DNA into functional chromatin is acquired during meiotic maturation in murine oocytes.在小鼠卵母细胞减数分裂成熟过程中获得了将精子DNA组织成功能性染色质的能力。
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The Drosophila maternal gene sésame is required for sperm chromatin remodeling at fertilization.果蝇母体基因芝麻在受精时对精子染色质重塑是必需的。
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Paternal pronuclear DNA degradation is functionally linked to DNA replication in mouse oocytes.父本原核DNA降解在功能上与小鼠卵母细胞中的DNA复制相关联。
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The sperm nuclear matrix is required for paternal DNA replication.父本DNA复制需要精子核基质。
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Mouse zygotes respond to severe sperm DNA damage by delaying paternal DNA replication and embryonic development.鼠受精卵通过延迟父源 DNA 复制和胚胎发育来应对严重的精子 DNA 损伤。
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Intracytoplasmic sperm injection for Rhesus monkey fertilization results in unusual chromatin, cytoskeletal, and membrane events, but eventually leads to pronuclear development and sperm aster assembly.恒河猴受精的胞浆内单精子注射会导致异常的染色质、细胞骨架和膜事件,但最终会导致原核发育和精子星体组装。
Hum Reprod. 1996 Aug;11(8):1703-12. doi: 10.1093/oxfordjournals.humrep.a019473.

本文引用的文献

1
BRIT1/MCPH1 is essential for mitotic and meiotic recombination DNA repair and maintaining genomic stability in mice.BRIT1/MCPH1 对于有丝分裂和减数分裂重组 DNA 修复以及维持小鼠的基因组稳定性是必需的。
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Factors engaged in reactivation of DNA replication in the nuclei of growing mouse oocytes introduced into the cytoplasm of parthenogenetic one-cell embryos.引入孤雌生殖单细胞胚胎细胞质中的生长小鼠卵母细胞核内参与DNA复制重新激活的因素。
Int J Dev Biol. 2010;54(1):21-31. doi: 10.1387/ijdb.092873eb.
3
A novel nuclease activity that is activated by Ca(2+) chelated to EGTA.一种新型核酸酶活性,可被螯合 EGTA 的 Ca(2+) 激活。
Syst Biol Reprod Med. 2009 Dec;55(5-6):193-9. doi: 10.3109/19396360903234052.
4
Asynchronous DNA replication and origin licensing in the mouse one-cell embryo.小鼠单细胞胚胎中的异步DNA复制与复制起点许可
J Cell Biochem. 2009 May 15;107(2):214-23. doi: 10.1002/jcb.22117.
5
Interaction between HMGA1a and the origin recognition complex creates site-specific replication origins.HMGA1a与复制起点识别复合体之间的相互作用产生位点特异性复制起点。
Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1692-7. doi: 10.1073/pnas.0707260105. Epub 2008 Jan 30.
6
Mouse spermatozoa contain a nuclease that is activated by pretreatment with EGTA and subsequent calcium incubation.小鼠精子含有一种核酸酶,该酶可通过用乙二醇双(2-氨基乙基醚)四乙酸(EGTA)预处理并随后进行钙孵育来激活。
J Cell Biochem. 2008 Apr 1;103(5):1636-45. doi: 10.1002/jcb.21549.
7
Paternal pronuclear DNA degradation is functionally linked to DNA replication in mouse oocytes.父本原核DNA降解在功能上与小鼠卵母细胞中的DNA复制相关联。
Biol Reprod. 2007 Sep;77(3):407-15. doi: 10.1095/biolreprod.107.061473. Epub 2007 May 9.
8
The sperm nuclear matrix is required for paternal DNA replication.父本DNA复制需要精子核基质。
J Cell Biochem. 2007 Oct 15;102(3):680-8. doi: 10.1002/jcb.21321.
9
The elusive determinants of replication origins.复制起点难以捉摸的决定因素。
EMBO Rep. 2007 Apr;8(4):332-4. doi: 10.1038/sj.embor.7400954.
10
Topoisomerase II-mediated breaks in spermatozoa cause the specific degradation of paternal DNA in fertilized oocytes.拓扑异构酶II介导的精子断裂导致受精卵中父本DNA的特异性降解。
Biol Reprod. 2007 Apr;76(4):666-72. doi: 10.1095/biolreprod.106.057067. Epub 2006 Dec 20.