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DNA polymerase eta (RAD30 homolog A, xeroderma pigmentosum variant type protein, POLH, RAD30, RAD30A, XPV)
Function:
- DNA polymerase specifically involved in DNA repair
- role in translesion synthesis, where normal high fidelity DNA polymerases cannot proceed & DNA synthesis stalls
- role in the repair of UV-induced pyrimidine dimers
- depending on the context, it inserts the correct base, but causes frequent base transitions & transversions
- may play a role in hypermutation at immunoglobulin genes
- forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity
- targets POLI to replication foci
- binds REV1L (putative)
- binds monoubiquitinated PCNA, but not unmodified PCNA
- binds POLI
Cofactor:
- divalent metal cations
- prefers Mg+2, but can also use Mn+2
Structure:
- catalytic core consists of fingers, palm & thumb subdomains, but the fingers & thumb subdomains are much smaller than in high-fidelity polymerases
- residues from five sequence motifs of the Y-family cluster around an active site cleft that can accommodate DNA & nucleotide substrates with relaxed geometric constraints, with consequently higher rates of misincorporation & low processivity
- belongs to the DNA polymerase type-Y family
- contains 1 umuC domain
Compartment:
- nucleus
- accumulates at replication forks after DNA damage
Alternative splicing: named isoforms=2
Pathology:
- defects in POLH are the cause of xeroderma pigmentosum variant type (XPV)
Related
xeroderma pigmentosum
General
DNA polymerase
Properties
SIZE: entity length = 713 aa
MW = 78 kD
COMPARTMENT: cell nucleus
MOTIF: UmuC {9-259}
MOTIF: Mg+2-binding site
SITE: 13-13
Mg+2-binding site
SITE: 115-115
Ser phosphorylation site {S379}
Ser phosphorylation site {S380}
Database Correlations
OMIM correlations
MORBIDMAP 603968
UniProt Q9Y253
Pfam PF00817
Kegg hsa:5429
ENZYME 2.7.7.7
References
- UniProt :accession Q9Y253
- Atlas of genetics & cytogenetics in oncology & haematology
http://atlasgeneticsoncology.org/genes/XPVID303.html
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=POLH
- Allelic variations of the XP genes
http://www.xpmutations.org/