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] 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]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000051341 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034206 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 10395804.
- ^ "Entrez Gene: POLQ polymerase (DNA directed), theta".
- PMID 20617203.
- PMID 20460465.
- PMID 24496117.
- PMID 24614976.
- S2CID 195892718.
- PMID 25275444.
- PMID 25642960.
- PMID 25642963.
- S2CID 195892718.
- ^ "New discovery shows human cells can write RNA sequences into DNA". phys.org. Retrieved 10 July 2021.
- PMID 34117057.
Further reading
- Hogg M, Sauer-Eriksson AE, Johansson E (March 2012). "Promiscuous DNA synthesis by human DNA polymerase θ". Nucleic Acids Research. 40 (6): 2611–22. PMID 22135286.
- Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, Bieber FR, Morton CC (September 1994). "Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening". Genomics. 23 (1): 42–50. PMID 7829101.
- Maga G, Shevelev I, Ramadan K, Spadari S, Hübscher U (May 2002). "DNA polymerase theta purified from human cells is a high-fidelity enzyme". Journal of Molecular Biology. 319 (2): 359–69. PMID 12051913.
- Seki M, Marini F, Wood RD (November 2003). "POLQ (Pol theta), a DNA polymerase and DNA-dependent ATPase in human cells". Nucleic Acids Research. 31 (21): 6117–26. PMID 14576298.
- Kawamura K, Bahar R, Seimiya M, Chiyo M, Wada A, Okada S, et al. (March 2004). "DNA polymerase theta is preferentially expressed in lymphoid tissues and upregulated in human cancers". International Journal of Cancer. 109 (1): 9–16. S2CID 19912440.
- Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, et al. (September 2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions". Genome Research. 14 (9): 1711–8. PMID 15342556.
- Seki M, Masutani C, Yang LW, Schuffert A, Iwai S, Bahar I, Wood RD (November 2004). "High-efficiency bypass of DNA damage by human DNA polymerase Q". The EMBO Journal. 23 (22): 4484–94. PMID 15496986.
- Chiapperino D, Cai M, Sayer JM, Yagi H, Kroth H, Masutani C, et al. (December 2005). "Error-prone translesion synthesis by human DNA polymerase eta on DNA-containing deoxyadenosine adducts of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene". The Journal of Biological Chemistry. 280 (48): 39684–92. PMID 16188888.
- Zan H, Shima N, Xu Z, Al-Qahtani A, Evinger Iii AJ, Zhong Y, et al. (November 2005). "The translesion DNA polymerase theta plays a dominant role in immunoglobulin gene somatic hypermutation". The EMBO Journal. 24 (21): 3757–69. PMID 16222339.
- Cruet-Hennequart S, Coyne S, Glynn MT, Oakley GG, Carty MP (April 2006). "UV-induced RPA phosphorylation is increased in the absence of DNA polymerase eta and requires DNA-PK". DNA Repair. 5 (4): 491–504. PMID 16520097.
- Chen YW, Cleaver JE, Hanaoka F, Chang CF, Chou KM (April 2006). "A novel role of DNA polymerase eta in modulating cellular sensitivity to chemotherapeutic agents". Molecular Cancer Research. 4 (4): 257–65. PMID 16603639.
- Yuasa MS, Masutani C, Hirano A, Cohn MA, Yamaizumi M, Nakatani Y, Hanaoka F (July 2006). "A human DNA polymerase eta complex containing Rad18, Rad6 and Rev1; proteomic analysis and targeting of the complex to the chromatin-bound fraction of cells undergoing replication fork arrest". Genes to Cells. 11 (7): 731–44. S2CID 32695133.
- Choi JY, Stover JS, Angel KC, Chowdhury G, Rizzo CJ, Guengerich FP (September 2006). "Biochemical basis of genotoxicity of heterocyclic arylamine food mutagens: Human DNA polymerase eta selectively produces a two-base deletion in copying the N2-guanyl adduct of 2-amino-3-methylimidazo[4,5-f]quinoline but not the C8 adduct at the NarI G3 site". The Journal of Biological Chemistry. 281 (35): 25297–306. PMID 16835218.
- Kino K, Ito N, Sugasawa K, Sugiyama H, Hanaoka F (2007). "Translesion synthesis by human DNA polymerase eta across oxidative products of guanine". Nucleic Acids Symposium Series. 48 (48): 171–2. PMID 17150533.
- Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. PMID 17353931.
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