TLSpolymeraasit

TLSpolymeraasit, often referred to as TLS polymerases or translesion synthesis polymerases, are a unique class of enzymes found in all domains of life. Their primary function is to replicate DNA across damaged templates, a process crucial for maintaining genome stability. Unlike high-fidelity replicative polymerases that stall or induce cell death when encountering DNA lesions, TLS polymerases are specialized to bypass these impediments. They achieve this by possessing a larger active site, which allows them to accommodate the altered geometry of a damaged nucleotide, and by exhibiting lower fidelity. This lower fidelity means they are more prone to incorporating incorrect nucleotides opposite a lesion, but this error-proneness is a trade-off for the cell's ability to survive DNA damage.

The mechanism of TLS involves the recruitment of TLS polymerases to stalled replication forks. Once at the lesion, they can insert a nucleotide opposite the damage. While some TLS polymerases can also extend the DNA chain across the lesion, others hand off the replication process back to the high-fidelity replicative polymerase once the lesion is bypassed. This coordination ensures that the genome can be replicated even in the presence of DNA damage, albeit with a controlled level of mutagenesis. This mutagenic potential of TLS polymerases can be both beneficial, by allowing cells to adapt to adverse conditions, and detrimental, by contributing to the development of diseases like cancer. Understanding TLS polymerases is therefore important for both fundamental biology and for therapeutic strategies.