Replication Repair

未修复的DNA损伤可能导致细胞死亡或突变，其中任何一种都可能造成严重的健康后果。经典定义的DNA修复机制是损伤的直接逆转、损伤的切除随后受损链的再合成、绕过损伤而不去除损伤的剪切-粘贴重组过程以及诱变性损伤合成。一种新的类似重组的机制叫做？复制修复？是多年前假设的，最近在噬菌体T4中使用遗传学和酶学方法表征。两个平行的途径似乎运作，一个采用T4 SSB和复制解旋酶和其他的T4重组酶和不同的解旋酶。在每个途径中，封闭的引物末端切换到另一个子链，将其短暂地用作模板，然后切换回绕过DNA损伤的同源亲本链。这种模板转换机制避免了在跨损伤合成过程中可能出现的突变。然而，有一小类突变通常在单个事件中产生多个突变，这些突变与各种重复序列相关，并且似乎是模板化的。像复制修复一样，这些突变被建模为模板转换的产物，但异位模板可以是不完美反向重复序列（准回文）附近的另一条亲本链。因此，我们正在研究是否突变，损害复制修复也影响模板诱变。

Unrepaired DNA damage can result in cell death or mutation, either of which can have serious health consequences. The classically defined mechanisms of DNA repair are direct reversal of the damage, excision of the damage followed by resynthesis of the damaged strand, a cut-and-paste recombinational process that bypasses the damage without removing it, and mutagenic translesion synthesis. A new recombination-like mechanism called ?replication repair? was postulated many years ago and was characterized recently in bacteriophage T4 using both genetic and enzymological methods. Two parallel pathways seem to operate, one employing the T4 SSB and replicative helicase and the other the T4 recombinase and a different helicase. In each pathway, a blocked primer terminus switches to the other daughter strand, uses it briefly as a template, and then switches back to the cognate parental strand having bypassed the DNA damage. This template-switching mechanism avoids the mutations that might otherwise arise during translesion synthesis. However, there is a minor class of mutations that often generates multiple mutations in a single event, mutations that are associated with various kinds of repeated sequences and that seem to be templated. Like replication repair, these mutations are modeled as the products of template switching, but the ectopic template can be the other parental strand in the neighborhood of an imperfect reverse repeat (a quasipalindrome). We are therefore investigating whether mutations that impair replication repair also affect templated mutagenesis.