Search results for POLH

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Reaction (10 results from a total of 10)

Identifier: R-HSA-110319
Species: Homo sapiens
Compartment: nucleoplasm
After incorporating two dAMPs opposite the thymine-thymine cyclobutane pyrimidine dimer (TT-CPD), DNA polymerase eta (POLH) can continue translesion DNA synthesis (TLS). POLH preferentially incorporates dAMPs and dGMPs, and may introduce one error per every 18-380 nucleotides (dNMPs) added. POLH stalls after incorporation of a mispaired dNMP, which limits POLH- mediated mutagenesis, in addition to the subsequent polymerase switch (Matsuda et al. 2000, Masutani et al. 2000).
Identifier: R-HSA-5655170
Species: Homo sapiens
Compartment: nucleoplasm
RCHY1 (Pirh2) acts as an E3 ubiquitin ligase to monoubiquitinate POLH (DNA polymerase eta) on lysine residues K682, K686, K694 and K709 located in the NLS (nuclear localization signal) of POLH (Jung et al. 2011). The NLS sequence of POLH is located between UBZ domain and PIP box, involved in POLH binding to monoubiquitinated PCNA (MonoUb:K164-PCNA). POLH monoubiquitination masks the PCNA-interaction region, thus disabling POLH binding to MonoUb:K164-PCNA and preventing POLH-mediated translesion DNA synthesis (TLS) (Bienko et al. 2010).
Identifier: R-HSA-5655142
Species: Homo sapiens
Compartment: nucleoplasm
RCHY1 (Pirh2) is an E3 ubiquitin ligase that binds DNA polymerase eta (POLH). This interaction involves the polymerase-associated domain of POLH and the RING finger of RCHY1 (Jung et al. 2010).
Identifier: R-HSA-5654989
Species: Homo sapiens
Compartment: nucleoplasm
The ATP-ase activity of VCP facilitates release of POLH (DNA polymerase eta) from monoubiquitinated PCNA (MonoUb:K164-PCNA) at DNA damage sites, thus ending POLH-mediated translesion DNA synthesis (TLS) (Davis et al. 2012, Mosbech et al. 2012). Although conjugation of the ubiquitin-like protein ISG15 to PCNA has been found to terminate POLH-dependent TLS, the SPRTN:VCP complex has been implicated in serving as an alternative termination pathway (Park et al. 2014). Since VCP has been found to undergo ISGylation (Giannakopoulos et al. 2005), it remains to be determined whether SPRTN, VCP and the ISG15-conjugating system function in the same TLS-regulatory pathway or two separate pathways.
Identifier: R-HSA-5654986
Species: Homo sapiens
Compartment: nucleoplasm
SPRTN (Spartan, C1orf124, DVC1) contains a PIP box and a UBZ domain that both participate in binding to monoubiquitinated PCNA (MonoUb:K164-PCNA), thus regulating POLH-mediated translesion DNA synthesis (TLS). The SPRTN UBZ domain may also interact with other monoubiquitinated proteins at the site of DNA damage. SPRTN can also bind RAD18 and function in a positive feedback loop to increase (or maintain) PCNA monoubiquitination (Centore et al. 2012, Ghosal et al. 2012).


Endogenous SPRTN is predominantly expressed during S and G2 phases of the cell cycle, and is rapidly degraded by the APC:CDH1 complex at mitotic exit (Mosbech et al. 2012).

Identifier: R-HSA-110317
Species: Homo sapiens
Compartment: nucleoplasm
DNA polymerase eta (POLH) correctly incorporates two adenine deoxyribonucleotides (dAMPs) opposite a TT-CPD (thymine-thymine cyclobutane pyrimidine dimer) lesion. POLH can bypass other types of lesions, such as AP sites and cisplatin-induced intrastrand cross-linked gunanines, preferentially incorporating dAMPs and dGMPs opposite the lesion. While POLH is accurate in translesion synthesis (TLS) across thymine dimers, POLH has a low fidelity in TLS across other DNA damage types and when copying undamaged DNA. One of the protective mechanisms against POLH-induced mutagenesis may be that POLH cannot continue chain elongation after an incorrect nucleotide is incorporated (Matsuda et al. 2000, Masutani et al. 2000).
Identifier: R-HSA-5654985
Species: Homo sapiens
Compartment: nucleoplasm
SPRTN (Spartan, C1orf124, DVC1) contains a SHP box that binds the hexameric AAA-ATPase VCP (p97). SPRTN recruits VCP, in complex with VCP adaptors NPLOC4 and UFD1L, to monoubiquitinated PCNA (MonoUb:K164-PCNA) associated with POLH at DNA damage sites (Ghosal et al. 2012, Davis et al. 2012, Mosbech et al. 2012).
Identifier: R-HSA-110316
Species: Homo sapiens
Compartment: nucleoplasm
DNA polymerase eta (POLH) belongs to Y family of DNA polymerases. POLH binds PCNA monoubiquitinated at lysine K164 by the RAD18:UBE2B (RAD18:RAD6) or RBX1:CUL4:DDB1:DTL complexes in response to DNA damage. POLH C-terminus contains a conserved PCNA interaction motif, while the catalytic domain of POLH contains a conserved monoubiquitin binding motif. POLH is most efficient in recognition and repair of thymine-thymine cyclobutane pyrimidine dimers (TT-CPD) induced by UV-mediated DNA damage (Masutani et al. 2000, Kannouche et al. 2004)
Identifier: R-HSA-5655193
Species: Homo sapiens
Compartment: nucleoplasm
KIAA0101 (PAF15) is a PCNA-associated protein expressed during S phase of the cell cycle, under the control of members of the E2F transcription factor family (Chang et al. 2013) and degraded at mitotic exit by the APC:CDH1 complex (Emanuele et al. 2011). KIAA0101 is monoubiquitinated on two lysine residues, K15 and K24, by an unknown ubiquitin ligase. Doubly monoubiquitinated KIAA0101 (PAF15) (MonoUb:K15,K24-KIAA0101) binds PCNA and promotes the switch from translesion DNA synthesis (TLS) polymerase, such as DNA polymerase eta (POLH), to replicative DNA polymerases delta (POLD) or epsilon (POLE). KIAA0101 monoubiquitination thus facilitates termination of TLS and coordinates DNA damage bypass events (Povlsen et al. 2012). UV-induced DNA damage causes removal of MonoUb:K15,K24-KIAA0101 by proteasome-mediated degradation, promoting the switch from replicative DNA polymerase complexes delta (POLD) or epsilon (POLE) to translesion DNA synthesis (TLS) polymerases, such as POLH (DNA polymerase eta) (Povlsen et al. 2012).
Identifier: R-HSA-5693593
Species: Homo sapiens
Compartment: nucleoplasm
Following branch migration, the invading 3' resected ssDNA end of the double-strand break (DSB) acts as a primer for repair DNA synthesis using the complementary strand of the invaded duplex as a template. The replicative DNA polymerases delta (POLD) and likely epsilon (POLE), as well as translesion synthesis (TLS) DNA polymerases eta (POLH) and kappa (POLK) in complex with PCNA, RFC and RPA are implicated in DNA repair synthesis and D-loop extension. While TLS polymerases increase the efficiency of homologous recombination-related DNA synthesis and can directly interact with D-loop proteins RAD51, PALB2 and BRCA2, it is likely that replicative DNA polymerases POLD and POLE, with their high processivity and fidelity, perform the major role in D-loop extension (McIlwraith et al. 2005, Sebesta et al. 2013, Pomerantz et al. 2013, Buisson et al. 2014). In addition, the presence of RAD51-translocases, homologous to yeast Rad54, that remove RAD51 from the 3' invading strand, may be necessary for the catalytic activity of POLD or POLE (Li et al. 2009, Li and Heyer 2009).
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