Replication Repair

未修复的DNA损伤可导致细胞死亡或突变，这两种情况都可能对健康造成严重后果。经典定义的DNA修复机制是损伤的直接逆转，损伤的切除随后是受损链的重新合成，剪切-粘贴重组过程绕过损伤而不去除它，以及诱变翻译合成。一种新的类似重组的机制叫做？复制修复吗?多年前被假设，最近在T4噬菌体中使用遗传和酶学方法进行了表征。两种平行的途径似乎起作用，一种使用T4 SSB和复制解旋酶，另一种使用T4重组酶和不同的解旋酶。在每一条途径中，被阻断的引物末端切换到另一条子链上，短暂地将其用作模板，然后切换到绕过DNA损伤的同源亲本链上。这种模板转换机制避免了翻译合成过程中可能出现的突变。然而，有一小类突变通常在一个事件中产生多个突变，这些突变与各种重复序列相关，似乎是模板化的。像复制修复一样，这些突变被建模为模板切换的产物，但异位模板可以是不完美反向重复附近的另一条亲本链（准平行重复）。因此，我们正在研究损害复制修复的突变是否也会影响模板诱变。

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.