DNA polymerase beta

Polymerase (DNA directed), beta, also known as POLB, is an is_associated_with::enzyme that, in humans, is encoded by the POLB is_associated_with::gene.

Function
In eukaryotic cells, DNA polymerase beta (POLB) performs is_associated_with::base excision repair (BER) required for is_associated_with::DNA maintenance, replication, recombination, and drug resistance.

Regulation of expression
DNA polymerase beta maintains genome integrity by participating in is_associated_with::base excision repair. Overexpression of POLB is_associated_with::mRNA has been correlated with a number of cancer types, whereas deficiencies in POLB results in hypersensitivity to is_associated_with::alkylating agents, induced is_associated_with::apoptosis, and chromosomal breaking [ref7]. Therefore, it is essential that POLB expression is tightly regulated.

POLB gene is upregulated by is_associated_with::CREB1 is_associated_with::transcription factor's binding to the is_associated_with::cAMP response element(CRE) present in the promoter of the POLB gene in response to exposure to alkylating agents. POLB gene expression is also regulated at the post transcriptional level as the 3’UTR of the POLB mRNA has been shown to contain three is_associated_with::stem-loop structures that influence gene expression. These three-stem loop structures are known as M1, M2, and M3, where M2 and M3 have a key role in gene regulation. M3 contributes to gene expression, as it contains the is_associated_with::polyadenylation signal followed by the cleavage and polyadenylation site, thereby contributing to is_associated_with::pre-mRNA processing. M2 has been shown to be evolutionary conserved, and, through mutagenesis, it was shown that this stem loop structure acts as a RNA destabilizing element.

In addition to these is_associated_with::cis-regulatory elements present within the 3’UTR a is_associated_with::trans-acting protein, is_associated_with::HAX1 is thought to contribute to the regulation of gene expression. Yeast three-hybrid assays have shown that this protein binds to the stem loops within the 3’UTR of the POLB mRNA, however the exact mechanism in how this protein regulates gene expression is still to be determined.

Interactions
DNA polymerase beta has been shown to interact with is_associated_with::PNKP and is_associated_with::XRCC1.

Model organisms
is_associated_with::Model organisms have been used in the study of POLB function. A conditional is_associated_with::knockout mouse line called Polbtm1a(KOMP)Wtsi was generated at the is_associated_with::Wellcome Trust Sanger Institute. Male and female animals underwent a standardized is_associated_with::phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping

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