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Kinetic and Structural Impact of Metal Ions and Genetic Variations on Human DNA Polymerase iota.
Germline genetic variations in human POLI gene may either hinder or promote the translesion synthesis (TLS (zeige FUS Proteine)) capability of pol iota (zeige POLM Proteine) with various DNA lesions in vitro, emphasizing the potential translational importance of these pol iota (zeige POLM Proteine) genetic variations, e.g., individual differences in TLS (zeige FUS Proteine), mutation, and cancer susceptibility to genotoxic carcinogens.
a single residue in pol iota (zeige POLM Proteine) is able to discriminate between NTPs and dNTPs during DNA synthesis.
Dysregulation of pol iota (zeige POLM Proteine) by JNK/c-Jun is involved in carcinogenesis and offer a novel understanding of the role of pol iota (zeige POLM Proteine) or c-Jun (zeige JUN Proteine) in mutagenesis.
Human Pol iota and yeast Pol zeta complex could function efficiently in the insertion and extension steps, respectively, of ranslesion synthesis and human Pol kappa and Pol eta could also extend past these lesions, albeit much less efficiently.
POLI and MC4R (zeige MC4R Proteine) nearby single nucleotide polymorphisms in human chromosome 18 are associated with a moderate risk of type 2 diabetes.
Results show that the physical and functional interaction between pols eta and iota occurs between ubiquitinated forms of either polymerase via their respective ubiquitin-binding domains.
this review briefly discusses the main structural features and possible functional mechanisms of the active center of Pol iota (zeige POLM Proteine). [review]
structural mechanism of high-fidelity 8-oxo-G replication by a human DNA polymerase (zeige POLB Proteine)
Structural basis for proficient incorporation of dTTP opposite O6-methylguanine by human DNA polymerase iota.
Pol iota occasionally accesses the replication fork to generate a first mutation, and Pol zeta extends the mismatch with a second mutation.
Mouse DNA polymerase iota lacking exon 2 (42 amino acids) is catalytically inactive in vitro.
Exon 2 deletion abrogates both the DNA polymerase (zeige POLB Proteine) and dRP lyase activities of Pol iota in the presence of either Mg(2 (zeige MCOLN1 Proteine)+) or Mn(2+) ions. Thus, 129-derived strains of mice express catalytically inactive alternatively spliced Pol iota variant.
PolH (zeige POLH Proteine) contributes to accurate translesion synthesis (TLS (zeige FUS Proteine)) past both T- & C-containing dimers. PolI is involved in error-prone TLS (zeige FUS Proteine) past cytosine-containing dimers when Poleta is inactivated.
Poliota causes the Par2 (zeige F2RL1 Proteine) effect and inhibits tumorigenesis and mutagenesis
Upon DNA damage, the UBDs (UBM domains) of polymerase iota (Pol iota) interact with ubiquitinated proliferating cell nuclear antigen (zeige PCNA Proteine) to regulate the interchange between processive DNA polymerases and translesional synthesis
In the presence of Mg2 (zeige MCOLN1 Proteine)+, the enzyme was active only in testicles and brain, whereas in the presence of Mn2+ the activity was found in all organs.
Data suggest that either DNA polymerase iota does not participate in hypermutation, or its role is nonessential and can be readily assumed by another low-fidelity polymerase.
Nucleotide polymorphisms in DNA polymerase iota is associated with lung tumorigenesis in mouse and humans
Pol kappa (zeige POLL Proteine) and Pol iota double-deficient mice had the normal somatic hypermutation frequency
Error-prone DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Favors Hoogsteen base-pairing in the active site. Inserts the correct base with high-fidelity opposite an adenosine template. Exhibits low fidelity and efficiency opposite a thymidine template, where it will preferentially insert guanosine. May play a role in hypermutation of immunogobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but may not have lyase activity (By similarity).
DNA polymerase iota
, polymerase (DNA directed) iota
, DNA polymerase iota-like
, RAD30 homolog B
, polymerase (DNA-directed), iota