Ren Keqin, Peña de Ortiz Sandra
Department of Biology, University of Puerto Rico, San Juan, Puerto Rico.
J Neurochem. 2002 Mar;80(6):949-59. doi: 10.1046/j.0022-3042.2002.00776.x.
Recent evidence suggests that DNA double strand breaks (DSBs) are introduced in neurons during the course of normal development, and that repair of such DSBs is essential for neuronal survival. Here we describe a non-homologous DNA end joining (NHEJ) system in the adult rat brain that may be used to repair DNA DSBs. In the brain NHEJ system, blunt DNA ends are joined with lower efficiency than cohesive or non-matching protruding ends. Moreover, brain NHEJ is blocked by DNA ligase inhibitors or by dATP and can occur in the presence or absence of exogenously added ATP. Comparison of NHEJ activities in several tissues showed that brain and testis share similar mechanisms for DNA end joining, whereas the activity in thymus seems to utilize different mechanisms than in the nervous system. The developmental profile of brain NHEJ showed increasing levels of activity after birth, peaking at postnatal day 12 and then gradually decreasing along with age. Brain distribution analysis in adult animals showed that NHEJ activity is differentially distributed among different regions. We suggest that the DNA NHEJ system may be utilized in the postnatal brain for the repair of DNA double strand breaks introduced within the genome in the postnatal brain.
最近的证据表明，在正常发育过程中神经元会出现DNA双链断裂（DSB），并且此类DSB的修复对于神经元存活至关重要。在此我们描述了成年大鼠脑中一种可能用于修复DNA DSB的非同源DNA末端连接（NHEJ）系统。在脑NHEJ系统中，平端DNA末端的连接效率低于粘性末端或不匹配的突出末端。此外，脑NHEJ会被DNA连接酶抑制剂或dATP阻断，并且在有无外源添加ATP的情况下均可发生。对几种组织中NHEJ活性的比较表明，脑和睾丸在DNA末端连接方面具有相似的机制，而胸腺中的活性似乎采用了与神经系统不同的机制。脑NHEJ的发育概况显示出生后活性水平不断升高，在出生后第12天达到峰值，然后随着年龄增长逐渐下降。成年动物的脑分布分析表明，NHEJ活性在不同区域差异分布。我们认为，DNA NHEJ系统可能在出生后的脑中用于修复出生后脑中基因组内引入的DNA双链断裂。
