Mekhail Karim
Department of Laboratory Medicine and Pathobiology, University of Toronto, MaRS Centre, Toronto, ON, Canada.
Canada Research Chairs Program, University of Toronto, Toronto, ON, Canada.
Front Genet. 2018 Mar 20;9:95. doi: 10.3389/fgene.2018.00095. eCollection 2018.
Eukaryotic genomes are non-randomly arranged inside the nucleus. Despite this ordered spatial genome organization, damaged DNA exhibits increased random mobility within nuclear space. This increased random movement is thought to promote DNA repair by facilitating homology search, allowing targeting to repair-conducive nuclear domains, or releasing damage from repair-repressive locations. Recent studies focusing on the relationship between telomeres, DNA repair processes, and nuclear organization have revealed that the disruption of motor proteins or microtubules, which typically mediate the directed motion of cargo, disrupts the random mobility of damaged DNA. These findings define a new biological paradox. Here, I define this as the damaged DNA mobility paradox, describe how it uncovers key gaps in knowledge, and highlight key questions to help guide us toward paradox resolution.
真核生物基因组在细胞核内呈非随机排列。尽管基因组存在这种有序的空间组织，但受损的DNA在核空间内的随机移动性却有所增加。这种增加的随机移动被认为通过促进同源性搜索、使靶向修复有利的核区域或从抑制修复的位置释放损伤来促进DNA修复。最近关注端粒、DNA修复过程和核组织之间关系的研究表明，通常介导货物定向运动的运动蛋白或微管的破坏会扰乱受损DNA的随机移动性。这些发现定义了一个新的生物学悖论。在此，我将其定义为受损DNA移动性悖论，描述它如何揭示知识上的关键空白，并突出关键问题以帮助引导我们解决这一悖论。
