Georgescu Roxana, Langston Lance, O'Donnell Mike
Rockefeller University and HHMI, 1230 York Avenue, Box 228, New York, NY 10065, United States.
Rockefeller University and HHMI, 1230 York Avenue, Box 228, New York, NY 10065, United States.
DNA Repair (Amst). 2015 May;29:4-15. doi: 10.1016/j.dnarep.2015.01.015. Epub 2015 Feb 9.
Processivity clamps that hold DNA polymerases to DNA for processivity were the first proteins known to encircle the DNA duplex. At the time, polymerase processivity was thought to be the only function of ring shaped processivity clamps. But studies from many laboratories have identified numerous proteins that bind and function with sliding clamps. Among these processes are mismatch repair and nucleosome assembly. Interestingly, there exist polymerases that are highly processive and do not require clamps. Hence, DNA polymerase processivity does not intrinsically require that sliding clamps evolved for this purpose. We propose that polymerases evolved to require clamps as a way of ensuring that clamps are deposited on newly replicated DNA. These clamps are then used on the newly replicated daughter strands, for processes important to genomic integrity, such as mismatch repair and the assembly of nucleosomes to maintain epigenetic states of replicating cells during development.
使DNA聚合酶与DNA结合以实现持续合成能力的持续合成能力钳是最早被发现能环绕DNA双链的蛋白质。当时,聚合酶的持续合成能力被认为是环形持续合成能力钳的唯一功能。但许多实验室的研究已经鉴定出众多与滑动钳结合并发挥作用的蛋白质。这些过程包括错配修复和核小体组装。有趣的是,存在一些具有高度持续合成能力且不需要钳的聚合酶。因此,DNA聚合酶的持续合成能力本质上并不要求滑动钳是为此目的而进化的。我们提出,聚合酶进化到需要钳,是作为一种确保钳沉积在新复制的DNA上的方式。然后这些钳在新复制的子链上用于对基因组完整性很重要的过程,比如错配修复以及在发育过程中组装核小体以维持复制细胞的表观遗传状态。