positive regulation of error-prone translesion synthesis

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of error-prone translesion synthesis. [GO_REF:0000058, GOC:kmv, GOC:TermGenie, PMID:22761594]

Positive regulation of error-prone translesion synthesis (TLS) is a complex cellular process that ensures DNA replication can continue despite the presence of DNA damage. This process involves specialized DNA polymerases that can bypass lesions that block the progression of the replicative DNA polymerases. However, these TLS polymerases often lack proofreading activity, leading to the introduction of mutations. This can be beneficial in some contexts, as it allows cells to bypass potentially lethal lesions, but it also poses a risk of introducing mutations that can lead to cancer.

The regulation of TLS is tightly controlled to ensure that it only occurs when necessary and to minimize the potential for mutagenesis. One key regulatory mechanism involves the recruitment of TLS polymerases to the site of DNA damage. This recruitment is mediated by a variety of factors, including PCNA (proliferating cell nuclear antigen) and specialized adaptor proteins. PCNA, a ring-shaped protein that encircles DNA, serves as a platform for the assembly of various proteins involved in DNA replication, including DNA polymerases. Damage recognition proteins, such as RAD6 and RAD18, are recruited to the site of DNA damage and modify PCNA through ubiquitination. This modification serves as a signal to recruit TLS polymerases to the damaged site.

Another level of regulation involves the activation of TLS polymerases. This can be achieved by various mechanisms, including phosphorylation and conformational changes. For example, ATR (ataxia telangiectasia mutated and Rad3-related) kinase, which is activated in response to DNA damage, phosphorylates the TLS polymerase REV1. This phosphorylation event promotes the recruitment of REV1 to the site of damage and facilitates its interaction with other TLS polymerases.

Finally, the termination of TLS is also tightly controlled. After the TLS polymerase has bypassed the lesion, the replicative polymerase must resume replication. This process involves the removal of the TLS polymerase and the replacement with the replicative polymerase. This switch is facilitated by a variety of factors, including PCNA ubiquitination status and the presence of specific DNA sequences.

In summary, the positive regulation of error-prone translesion synthesis is a multi-faceted process that involves the recruitment, activation, and termination of TLS polymerases. This complex regulatory network ensures that TLS is only activated when necessary and that it does not introduce an excessive number of mutations.'
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Proteins (2)

Compounds (6)