DNA polymerase eta

Definition:

DNA polymerase specifically involved in the DNA repair by translesion synthesis (TLS). Due to low processivity on both damaged and normal DNA, cooperates with the heterotetrameric (REV3L, REV7, POLD2 and POLD3) POLZ complex for complete bypass of DNA lesions. Inserts one or 2 nucleotide(s) opposite the lesion, the primer is further extended by the tetrameric POLZ complex. In the case of 1,2-intrastrand d(GpG)-cisplatin cross-link, inserts dCTP opposite the 3' guanine. Particularly important for the repair of UV-induced pyrimidine dimers. Although inserts the correct base, may cause base transitions and transversions depending upon the context. May play a role in hypermutation at immunoglobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have any lyase activity, preventing the release of the 5'-deoxyribose phosphate (5'-dRP) residue. This covalent trapping of the enzyme by the 5'-dRP residue inhibits its DNA synthetic activity during base excision repair, thereby avoiding high incidence of mutagenesis. Targets POLI to replication foci.

References:

[1]. E Glick, et al. Mutations in human DNA polymerase eta motif II alter bypass of DNA lesions. EMBO J. 2001 Dec 17;20(24):7303-12. [Content Brief]

[2]. C Masutani, et al. The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta. Nature. 1999 Jun 17;399(6737):700-4. [Content Brief]

[3]. Heather A Wallace, et al. TRIP/NOPO E3 ubiquitin ligase promotes ubiquitylation of DNA polymerase η. Development. 2014 Mar;141(6):1332-41. [Content Brief]

[4]. Marzena Bienko, et al. Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis. Science. 2005 Dec 16;310(5755):1821-4. [Content Brief]

[5]. X Zeng, et al. DNA polymerase eta is an A-T mutator in somatic hypermutation of immunoglobulin variable genes. Nat Immunol. 2001 Jun;2(6):537-41. [Content Brief]

[6]. Ahmad Faili, et al. DNA polymerase eta is involved in hypermutation occurring during immunoglobulin class switch recombination. J Exp Med. 2004 Jan 19;199(2):265-70. [Content Brief]

[7]. Lajos Haracska, et al. A mechanism for the exclusion of low-fidelity human Y-family DNA polymerases from base excision repair. Genes Dev. 2003 Nov 15;17(22):2777-85. [Content Brief]

[8]. Patricia Kannouche, et al. Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells. EMBO J. 2003 Mar 3;22(5):1223-33. [Content Brief]

[9]. Young-Sam Lee, et al. Human Pol ζ purified with accessory subunits is active in translesion DNA synthesis and complements Pol η in cisplatin bypass. Proc Natl Acad Sci U S A. 2014 Feb 25;111(8):2954-9. [Content Brief]

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