Tbio POLQ DNA polymerase theta

Protein Summary

Description

DNA polymerase that promotes microhomology-mediated end-joining (MMEJ), an alternative non-homologous end-joining (NHEJ) machinery triggered in response to double-strand breaks in DNA (PubMed:25642963, PubMed:25643323). MMEJ is an error-prone repair pathway that produces deletions of sequences from the strand being repaired and promotes genomic rearrangements, such as telomere fusions, some of them leading to cellular transformation (PubMed:25642963, PubMed:25643323). POLQ acts as an inhibitor of homology-recombination repair (HR) pathway by limiting RAD51 accumulation at resected ends (PubMed:25642963). POLQ-mediated MMEJ may be required to promote the survival of cells with a compromised HR repair pathway, thereby preventing genomic havoc by resolving unrepaired lesions (By similarity). The polymerase acts by binding directly the 2 ends of resected double-strand breaks, allowing microhomologous sequences in the overhangs to form base pairs. It then extends each strand from the base-paired region using the opposing overhang as a template. Requires partially resected DNA containing 2 to 6 base pairs of microhomology to perform MMEJ (PubMed:25643323). The polymerase activity is highly promiscuous: unlike most polymerases, promotes extension of ssDNA and partial ssDNA (pssDNA) substrates (PubMed:18503084, PubMed:21050863, PubMed:22135286). Also exhibits low-fidelity DNA synthesis, translesion synthesis and lyase activity, and it is implicated in interstrand-cross-link repair, base excision repair and DNA end-joining (PubMed:14576298, PubMed:18503084, PubMed:19188258, PubMed:24648516). Involved in somatic hypermutation of immunoglobulin genes, a process that requires the activity of DNA polymerases to ultimately introduce mutations at both A/T and C/G base pairs (By similarity).

Uniprot Accession IDs

• O75417
• O95160
• Q6VMB5

Gene Name

• POLQ

Ensembl ID

• ENST00000264233
• ENSP00000264233
• ENSG00000051341

Symbol

• POLH
• PRO0327

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	1
protein domain	0.97
histone modification site profile	0.89
transcription factor binding site profile	0.72
cell line	0.68

Protein Classes

PANTHER Classes

Protein / Transferase / Dna Polymerase Theta

Protein / Nucleic Acid Binding / Nuclease / Exodeoxyribonuclease / Dna Polymerase Theta

Protein / Nucleic Acid Binding / Dna Binding Protein / Exodeoxyribonuclease / Dna Polymerase Theta

Protein / Nucleic Acid Binding / Dna Binding Protein / Dna-directed Dna Polymerase / Dna Polymerase Theta

Protein / Hydrolase / Dna Polymerase Theta

DTO Classes

Protein / Enzyme / Transferase / Nucleotidyltransferase / Polymerase / Dna-directed Dna Polymerase / Dna Polymerase Theta

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 92.57   (req: < 5)

Gene RIFs: 53   (req: <= 3)

Antibodies: 69   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 92.57   (req: >= 5)

Gene RIFs: 53   (req: > 3)

Antibodies: 69   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 17

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0