POLQ

DNA polymerase theta is an enzyme that in humans is encoded by the POLQ gene.^[5][6] This polymerase plays a key role in one of the three major double strand break repair pathways: theta-mediated end joining (TMEJ).^{[7][8][9][10]} Most double-strand breaks are repaired by non-homologous end joining (NHEJ) or homology directed repair (HDR). However, in some contexts, NHEJ and HR are insufficient and TMEJ is the only solution to repair the break.^[11]

POLQ
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4X0P, 4X0Q, 5AGA, 5A9J, 5A9F
Identifiers
Aliases	POLQ, POLH, PRO0327, polymerase (DNA) theta, DNA polymerase theta, DNA polymerase θ
External IDs	OMIM: 604419; MGI: 2155399; HomoloGene: 32727; GeneCards: POLQ; OMA:POLQ - orthologs
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q13.33 Start 121,431,431 bp[1] End 121,545,988 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16 B3|16 26.32 cM Start 36,832,148 bp[2] End 36,915,779 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte testicle ventricular zone bone marrow ganglionic eminence bone marrow cells trabecular bone stromal cell of endometrium mucosa of transverse colon gingival epithelium Top expressed in tail of embryo genital tubercle morula spermatocyte ventricular zone yolk sac embryo zygote blastocyst secondary oocyte More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding DNA binding nucleotidyltransferase activity single-stranded DNA helicase activity 5'-deoxyribose-5-phosphate lyase activity chromatin binding damaged DNA binding protein binding nucleic acid binding DNA-directed DNA polymerase activity ATP binding 5'-3' exonuclease activity identical protein binding Cellular component nucleoplasm chromosome nucleus cytoplasm Biological process somatic hypermutation of immunoglobulin genes negative regulation of double-strand break repair via homologous recombination double-strand break repair via alternative nonhomologous end joining cellular response to DNA damage stimulus DNA replication double-strand break repair via homologous recombination protein homooligomerization DNA repair base-excision repair DNA biosynthetic process double-strand break repair DNA-dependent DNA replication nucleic acid phosphodiester bond hydrolysis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10721 77782 Ensembl ENSG00000051341 ENSMUSG00000034206 UniProt O75417 Q8CGS6 RefSeq (mRNA) NM_199420 NM_006596 NM_001159369 NM_029977 RefSeq (protein) NP_955452 NP_001152841 NP_084253 Location (UCSC) Chr 3: 121.43 – 121.55 Mb Chr 16: 36.83 – 36.92 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

TMEJ is often described as alternative NHEJ, but differs in that it lacks a requirement for the Ku heterodimer, and it can only act on resected DNA ends.^[12] Following annealing of short (i.e., a few nucleotides) regions on the DNA overhangs, DNA polymerase theta catalyzes template-dependent DNA synthesis across the broken ends, stabilizing the paired structure.^[13][14]

Polymerase theta's mutational signature

TMEJ is intrinsically mutagenic, since polymerase theta uses homologous nucleotides from both break ends to initiate repair, which leads to loss of one set of these nucleotides in the DNA sequence. Therefore, TMEJ is a form of micro-homology mediated end joining (MMEJ). Moreover, when break ends are not stabilized properly, the break ends can detach after polymerization. When these polymerized ends anneal again, a templated insert arises between the deletion junctions.^[15]

Reverse transcription of RNA

Polθ promotes RNA-templated DNA repair. Previously, DNA polymerases were long thought to only transcribe DNA into DNA or RNA and not be able to write RNA segments into DNA.^[16][17]