Mazzin Kamel

Abstract The ability of mutations to facilitate adaptation is central to evolution. To understand how mutations can lead to functional adaptation in a complex molecular machine, we created a defective version of the T4 clamp-loader complex, which is essential for DNA replication. This variant, which is ~5000-fold less active than the wildtype, was made by replacing the catalytic domains with those from another phage.

Abstract The ability of mutations to facilitate adaptation to changing conditions is central to evolution. The T4 bacteriophage clamp-loader complex, an oligomeric AAA+ ATPase required for processive DNA replication, is normally highly tolerant to most mutations. To study the adaptive capacity of the clamp loader, we created a chimeric version in which the catalytic AAA+ modules are replaced by those from another phage, resulting in a ~5000-fold reduction in phage replication rate.