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【bio-news】揭开DNA螺旋的蛋白复合体
Every second, the cells constituting our bodies are replaced through cell division. Researchers at Karolinska Institutet have found a piece of the puzzle of how genetic information remains intact despite this continuous exchange of cells. Their results are presented in the latest issue of the scientific journal Molecular Cell.
An adult human consists of about 50,000 billion cells, 1% of which die and are replaced by cell division every day. In order to ensure cell survival and controlled growth of these new cells, the genetic information, stored in DNA molecules, must first be correctly copied and then accurately distributed during cell division. Moreover, to fully ascertain that the new cells will contain the same genetic information as the parental cells, any damage to the DNA, which is organised into several chromosomes, must be repaired.
"A cancer cell often has chromosomal aberrations that can be linked to erroneous copying, separation, or repair of the DNA molecule. By learning about the normal mechanisms that maintain a stable genome we can gain a better position to understand what goes wrong in cancer", says Camilla Sjögren, who leads the research group.
Central to both chromosome repair and distribution during cell division are three related protein complexes.
"Quite a bit is known about two of these complexes. One of them, cohesin, keeps the DNA copies together such that they do not separate too early; while the other, condensin, makes the chromosomes more compact, making the separation easier", says Camilla Sjögren.
The research group has studied the third, less well understood, protein complex, known as the Smc5/6 complex. This protein complex was found to bind to locations on the DNA strand that the researchers had artificially damaged, suggesting that it is directly involved in the repair process. Moreover, the Smc5/6 complex also seems to be required for the disentanglement of undamaged chromosomes before cell division. If these tangles, which are a natural consequence of the DNA copying process, are left unresolved the chromosomes cannot be separated and sent to the two nascent daughter cells. Like in the repair process, the Smc5/6 complex appears to resolve these intertwines by direct interaction with the DNA molecules, but this process is differently regulated as compared to the function in repair.
"Evidence points to that the Smc5/6 complex work in two different pathways, one needed for repair and the other for untangling. We now aim to study how this works on a molecular level. This will bring us one step closer to the general goal – a summary of the many mechanisms that collaborate to maintain our genetic stability", says Camilla Sjögren.
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Reference:
"Chromosomal Association of the Smc5/6 Complex Reveals that it Functions in Differently Regulated Pathways"
Hanna Betts Lindroos, Lena Ström, Takehiko Itoh, Yuki Katou, Katsuhiko Shirahige and Camilla Sjögren.
Molecular Cell June 2006
For more information, please contact:
Group leader Camilla Sjögren, Department of Cell and Molecular Biology, Karolinska Institutet , Phone +46 8 5248 7761, Mobile: +46 708 2144 838, E-mail camilla.sjogren@ki.se 我翻译这篇 解开DNA螺旋的蛋白复合物
每秒钟，组成我们身体的细胞通过细胞分裂被更新。Karolinska研究所的研究人员发现了遗传信息是怎样在细胞连续替换的情况下仍然保持完整的部分谜底。他们的研究结果发表在最新一期的scientific journal Molecular Cell期刊上。
成年人的身体由500万亿细胞组成，每天有1%的细胞死亡，并被细胞分裂产生的新细胞所替代。为了确保细胞存活并控制这些新细胞的生长，DNA分子中储存的遗传信息必须首先被正确地复制，然后，在细胞分裂过程中正确地分布。此外，为了充分确定新细胞含有与双亲细胞完全一样的信息，任何对涉及到几个染色体的DNA损伤都必须被修复。
研究组领导Camilla Sjögren说“肿瘤细胞通常有与DNA分子异常的复制、分离或修复相关的染色体异常。通过发现维持基因组稳定的正常机制，我们能够更好地明白在癌细胞中什么出现了问题。”
在细胞分裂过程中，染色体修复和分布的核心是三个相关的蛋白复合物。
Camilla Sjögren说 “对三个蛋白复合物中的两个知道的相当多。一个是cohesin，保持DNA拷贝在一起，使它们不能分离得太早；而另一个，condensin使染色体保持紧凑，使染色体分离更容易。“
研究组已经对第三个蛋白复合体，就是通常所说的Smc5/6复合体，进行了研究，目前还不是很清楚。 这种蛋白复合体被发现能够结合到研究人员在DNA链上人为损伤的部位，提示了它与修复过程有直接关系。此外，Smc5/6蛋白复合体似乎也是在细胞分裂前解开没有损伤的染色体纠结所需要的。如果这些染色体复制过程的自然结果所造成的纠结没有被解开，染色体就不能被分离并送到两个子细胞中。就象在细胞修复过程，Smc5/6复合体似乎通过与DNA分子直接作用，解开了这些纠结，而这一过程与修复过程中的作用相比，Smc5/6蛋白复合体被不同地调控。
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作者:admin@医学,生命科学 2011-03-01 05:14
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