Shaman J A, Yamauchi Y, Ward W S
Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawaii, 1960 East-West Road, Honolulu, HI 96822, USA.
Biochem Soc Trans. 2007 Jun;35(Pt 3):626-8. doi: 10.1042/BST0350626.
We have recently demonstrated that mammalian spermatozoa have the ability to degrade their DNA by a mechanism that is similar to apoptosis in somatic cells. When this mechanism is activated, the DNA is first degraded into loop-sized fragments by TOP2B (topoisomerase IIB). This degradation, termed sperm chromatin fragmentation, can be reversed by EDTA, which causes TOP2B to religate the double-stranded breaks it originally produced. Under certain conditions, a nuclease then degrades the sperm DNA further, digesting the entire sperm genome. When mouse spermatozoa which have been treated to induce TOP2B-mediated DNA breaks are injected into oocytes, the paternal DNA is specifically and completely degraded. This total digestion of paternal DNA occurs at the time of DNA synthesis initiation. In the present study, we explore the significance of an active TOP2B in the nucleus for mouse sperm function.
我们最近证明，哺乳动物精子具有通过一种类似于体细胞凋亡的机制来降解其DNA的能力。当这种机制被激活时，DNA首先被TOP2B（拓扑异构酶IIB）降解成环状大小的片段。这种降解，称为精子染色质碎片化，可被EDTA逆转，EDTA会使TOP2B重新连接其最初产生的双链断裂。在某些条件下，一种核酸酶会进一步降解精子DNA，消化整个精子基因组。当经过处理以诱导TOP2B介导的DNA断裂的小鼠精子被注入卵母细胞时，父本DNA会被特异性且完全地降解。父本DNA的这种完全消化发生在DNA合成起始之时。在本研究中，我们探讨了细胞核中活跃的TOP2B对小鼠精子功能的重要性。
