A model for the control of DNA integrity by the sperm nuclear matrix.

A model for the control of DNA integrity by the sperm nuclear matrix.
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DOI:
10.4103/1008-682x.153853
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发表时间:
2015-07
影响因子:
2.9
通讯作者:
Ward WS
Ward WS
中科院分区:
医学2区
文献类型:
--
作者:
Gawecka JE;Ribas-Maynou J;Benet J;Ward WS

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哺乳动物精子的高度浓缩的染色质在受精前通常被认为是生物惰性的。然而,我们已经证明,即使在这种紧凑的状态下,精子染色质是受降解的开放配置与核基质通过一个过程,我们称之为精子染色质片段化(SCF)。这表明,存在一种机制来监测精子在通过男性生殖道期间的健康状况,并破坏有缺陷的精子细胞的基因组。SCF中的DNA损伤位点,即基质附着位点,与我们假设的合子中启动DNA合成的位点相同。当DNA受损的精子被注入卵母细胞时,新产生的受精卵会延迟雄性原核中的DNA合成,如果损伤足够严重,则会阻止胚胎的发育。在这里,我们提出了一个模型,父亲的DNA调控的核基质,在精子成熟过程中开始,并继续通过早期胚胎发育。
The highly condensed chromatin of mammalian spermatozoa is usually considered to be biologically inert before fertilization. However, we have demonstrated that even in this compacted state, sperm chromatin is subject to degradation at open configurations associated with the nuclear matrix through a process we have termed sperm chromatin fragmentation (SCF). This suggests that a mechanism exists to monitor the health of spermatozoa during transit through the male reproductive tract and to destroy the genome of defective sperm cells. The site of DNA damage in SCF, the matrix attachment sites, are the same that we hypothesize initiate DNA synthesis in the zygote. When sperm that have damaged DNA are injected into the oocyte, the newly created zygote responds by delaying DNA synthesis in the male pronucleus and, if the damage is severe enough, arresting the embryo's development. Here we present a model for paternal DNA regulation by the nuclear matrix that begins during sperm maturation and continues through early embryonic development.