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)

More general terms

• DNA polymerase

Additional terms

• xeroderma pigmentosum

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5429
• OMIM: https://mirror.omim.org/entry/603968
• OMIM: https://mirror.omim.org/entry/278750
• UniProt: http://www.uniprot.org/uniprot/Q9Y253.html