Regulating DNA supercoiling: sperm points the way.
Regulating DNA supercoiling: sperm points the way.
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调节 DNA 超螺旋：精子指明了道路。
DOI：
10.1095/biolreprod.111.090951
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发表时间：
2011
影响因子：
3.6
通讯作者：
Ward,WSteven
中科院分区：
文献类型：
--
作者：
Ward,WSteven
在伴随精子发生的染色质浓缩过程中，整个父本基因组不可避免地遭受大约 5 至 1000 万个双链 DNA 断裂（图 1A）。这些双链 DNA 断裂是由拓扑异构酶 (DNA) II beta (TOP2B)[1–3] 引起的，它是拓扑异构酶 II (TOP2) 的两种变体之一，它通过产生瞬时 DNA 双链断裂并使一条 DNA 链穿过断裂来解开和解开 DNA（见图 1B）[4, 5]。精子发生对降低超螺旋有独特的要求，因为组蛋白被去除，鱼精蛋白沉积在其位置上。这是因为鱼精蛋白结合 DNA 的超螺旋程度低于组蛋白结合 DNA；鱼精蛋白诱导更宽的超螺旋，比组蛋白更有效地将 DNA 包装到更小的空间中 [6, 7]（图 1A）。 TOP2B 可以缓解超螺旋，促进精子发生过程中组蛋白的移位。鉴于精子的主要功能是将父本基因组的原始副本传递给卵母细胞，然后在新形成的胚胎的生命周期中将其复制一万亿次，这一过程的发现自然会引起人们对如何对其进行调节以确保每次断裂都得到正确修复的担忧，这是可以理解的。例如，有人提出，男性不育的原因之一是成熟精子中残留的 DNA 双链断裂，这是由于精子发生过程中 TOP2B 不完整的 DNA 链传递造成的 [1, 8]。在本期中，Meyer-Ficca 等人[9]为精子发生过程中 DNA 断裂的调节提供了第一个证据。他们表明，每个 TOP2B 诱导的 DNA 双链断裂都需要聚（ADP-核糖）聚合酶 1（PARP1）和聚（ADP-核糖）糖水解酶（PARG）循环。由于两种 TOP2 变体之一普遍存在于所有细胞类型中，因此他们的结果对染色质结构也具有更广泛的影响。
During the chromatin condensation that accompanies spermiogenesis, the entire paternal genome suffers approximately 5 to 10 million double-strand DNA breaks as a matter of necessity (Fig. 1A). These double-strand DNA breaks are caused by topoisomerase (DNA) II beta (TOP2B)[1–3], one of two variants of topoisomerase II (TOP2), which unwinds and untangles DNA by creating a transient DNA double-strand break and passing one DNA strand through the break (see Fig. 1B)[4, 5]. Spermiogenesis has a unique requirement for decreased supercoiling as histones are removed and protamines are deposited in their place. This is because protamine-bound DNA is less supercoiled than histone-bound DNA; protamines induce wider supercoils that are more efficient for packing DNA into a smaller space than histones [6, 7](Fig. 1A). TOP2B relieves the supercoils, facilitating the displacement of histones during spermiogenesis. Given the fact that the main function of the spermatozoon is to deliver a pristine copy of the paternal genome to the oocyte that will then be copied a trillion times during the life of the newly formed embryo, the discovery of this process understandably lead to concerns about how it is regulated to ensure that every break is correctly repaired. It has been proposed, for example, that one cause of male infertility is residual DNA double-strand breaks in mature spermatozoa resulting from incomplete DNA strand passage by TOP2B during spermiogenesis [1, 8]. In this issue, Meyer-Ficca et al.[9] provide the first evidence for the regulation of this DNA breakage during spermiogenesis. They show that poly (ADP-ribose) polymerase 1 (PARP1) and poly (ADP-ribose) glycohydrolase (PARG) cycling is required for each TOP2B-induced DNA doublestrand break. Because one of the two TOP2 variants is ubiquitous in all cell types, their results also have wider implications for chromatin structure.