Search results for POLE

Showing 27 results out of 50

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Protein (5 results from a total of 5)

Identifier: R-HSA-68473
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: POLE: Q07864
Identifier: R-HSA-9647508
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: P21359
Identifier: R-HSA-68482
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: POLE2: P56282
Identifier: R-HSA-8866685
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: POLE3: Q9NRF9
Identifier: R-HSA-8866684
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: POLE4: Q9NR33

Set (4 results from a total of 4)

Identifier: R-HSA-5651800
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-5686084
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-6790535
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-6790534
Species: Homo sapiens
Compartment: nucleoplasm

Complex (6 results from a total of 17)

Identifier: R-HSA-6790531
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-6790530
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-5690470
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-5690478
Species: Homo sapiens
Compartment: nucleoplasm

Reaction (6 results from a total of 18)

Identifier: R-HSA-6782208
Species: Homo sapiens
Compartment: nucleoplasm
In transcription-coupled nucleotide excision repair (TC-NER), as well as in global genome nucleotide excision repair (GG-NER), the DNA synthesis complex (NER post-incision complex) consisting of PCNA, RPA, RFC and polymerase delta (POLD) or epsilon (POLE) complexes performs DNA repair synthesis after the damaged DNA strand is incised 5' to the lesion by the endonuclease complex ERCC1:ERCC4 (ERCC1:XPF) and 3' to the lesion by the endonuclease XPG (ERCC5). Depending on damage-induced PCNA monoubiquitination, DNA polymerase kappa (POLK) may also be involved in gap-filling DNA synthesis during nucleotide excision repair (NER) (Balajee et al. 1998, Staresincic et al. 2009, Ogi et al. 2010, Overmeer et al. 2011).
Identifier: R-HSA-5691001
Species: Homo sapiens
Compartment: nucleoplasm
In global genome nucleotide excision repair (GG-NER), as well as transcription-coupled nucleotide excision repair (TC-NER), the DNA synthesis complex consisting of PCNA, RPA, RFC and polymerase delta (POLD) or epsilon (POLE) complexes performs DNA repair synthesis after the damaged DNA strand is incised 5' to the lesion by the endonuclease complex ERCC1:ERCC4 (ERCC1:XPF) and 3' to the lesion by the endonuclease XPG (ERCC5). Depending on damage-induced PCNA monoubiquitination, DNA polymerase kappa (POLK) is also involved in gap-filling DNA synthesis during nucleotide excision repair (NER) (Balajee et al. 1998, Staresincic et al. 2009, Ogi et al. 2010, Overmeer et al. 2011).
Identifier: R-HSA-5653838
Species: Homo sapiens
Compartment: nucleoplasm
Once deubiquitinated and deISGylated, PCNA can again associate with the catalytic subunit POLD1 of replicative DNA polymerase delta complex (POLD), or presumably POLE of DNA polymerase epsilon complex (POLE) (Park et al. 2014). Double monoubiquitination of PCNA-associated protein KIAA0101 (PAF15) facilitates the switch from translesion DNA synthesis (TLS) polymerases to replicative DNA polymerases POLD or POLE (Povlsen et al. 2012).
Identifier: R-HSA-110368
Species: Homo sapiens
Compartment: nucleoplasm
Polymerase delta complex (POLD) or polymerase epsilon complex (POLE) bound to PCNA-associated replication complex that also includes RPA and RFC complexes, catalyzes DNA strand displacement synthesis in a reaction facilitated by FEN1 and APEX1. POLD or POLE extend the 3' end of the single strand break (SSB) by adding up to 10 nucleotides. The 5' end of the SSB, which contains the oxidatively damaged AP (apurinic/apyrimidinic) dideoxyribose phosphate residue (5'ddRP) that could not be excised by POLB, is displaced as a flap structure by the joint action of FEN1 and POLD or POLE (Klungland and Lindahl 1997, Stucki et al. 1998, Dianov et al. 1999, Podlutsky et al. 2001, Ranalli et al. 2002).
Identifier: R-HSA-5653840
Species: Homo sapiens
Compartment: nucleoplasm
After DNA damage is bypassed by error-prone DNA polymerases capable of translesion DNA synthesis (TLS), the replicative complex composed of PCNA, DNA polymerases delta (POLD) or epsilon (POLE), RPA and RFC, completes the replication of damaged DNA (Park et al. 2014). Replicated damaged DNA may then be repaired through base excision or another DNA repair mechanism before the next round of DNA replication.
Identifier: R-HSA-110364
Species: Homo sapiens
Compartment: nucleoplasm
PCNA-dependent long-patch base excision repair (BER) occurs during the S phase of the cell cycle when PCNA and associated DNA polymerases are available. PCNA is part of a large replicative complex that contains DNA polymerase delta or DNA polymerase epsilon, along with RPA and RFC complexes. When POLB (DNA polymerase beta) is unable to excise the oxidatively damaged AP residue (5'ddRP) at the APEX1-generated single strand break (SSB), PCNA and FEN1 are recruited to APEX1, where PCNA interacts with both APEX1 (Dianova et al. 2001) and FEN1 (Tom et al. 2000, Shibata and Nakamura 2002). PCNA-bound DNA polymerase delta complex (POLD) or DNA polymerase epsilon complex (POLE) displaces DNA polymerase beta (POLB) from the SSB (Klungland and Lindahl 1997).

Pathway (6 results from a total of 6)

Identifier: R-HSA-110314
Species: Homo sapiens
Compartment: nucleoplasm
Damaged double strand DNA (dsDNA) cannot be successfully used as a template by replicative DNA polymerase delta (POLD) and epsilon (POLE) complexes (Hoege et al. 2002). When the replication complex composed of PCNA, RPA, RFC and POLD or POLE stalls at a DNA damage site, PCNA becomes monoubiquitinated by RAD18 bound to UBE2B (RAD6). POLD or POLE dissociate from monoubiquitinated PCNA, while Y family DNA polymerases - REV1, POLH (DNA polymerase eta), POLK (DNA polymerase kappa) and POLI (DNA polymerase iota) - bind monoubiquitinated PCNA through their ubiquitin binding and PCNA binding motifs, resulting in a polymerase switch and initiation of translesion synthesis (TLS) (Hoege et al. 2002, Friedberg et al. 2005).
Identifier: R-HSA-5651801
Species: Homo sapiens
Compartment: nucleoplasm
Long-patch base excision repair (BER) can proceed through PCNA-dependent DNA strand displacement synthesis by replicative DNA polymerases - DNA polymerase delta complex (POLD) or DNA polymerase epsilon (POLE) complex. The PCNA-dependent branch of long-patch BER may occur in cells in the S phase of the cell cycle, when the replication complexes that contain PCNA, POLD or POLE, RPA and RFC are available. POLB incorporates the first nucleotide at the 3'-end of APEX1-generated single strand break (SSB), thus displacing the damaged AP (abasic) dideoxyribose phosphate residue at the 5'-end of SSB (5'ddRP). PCNA is recruited to BER sites by APEX1 and flap endonuclease FEN1, and loaded onto damaged DNA by RFC. POLD and POLE in complex with PCNA continue the displacement DNA strand synthesis. FEN1 cleaves the displaced DNA strand with the AP residue (5'ddRP), and DNA ligase I (LIG1) ligates the multiple nucleotide patch at the 3' end of the SSB with the FEN1-processed 5'-end of the SSB (Klungland and Lindahl 1997, Stucki et al. 1998, Dianov et al. 1999, Matsumoto et al. 1999, Podlutsky et al. 2001, Dianova et al. 2001, Ranalli et al. 2002).
Identifier: R-HSA-380320
Species: Homo sapiens
The NuMA protein, which functions as a nuclear matrix protein in interphase (Merdes and Cleveland 1998), redistributes to the cytoplasm following nuclear envelope breakdown where it plays an essential role in formation and maintenance of the spindle poles (Gaglio, et al., 1995; Gaglio, et al., 1996; Merdes et al, 1996). The mitotic activation of NuMA involves Ran-GTP-dependent dissociation from importin (Nachury et al, 2001, Wiese et al, 2001). NuMA is transported to the mitotic poles where it forms an insoluble crescent around centrosomes tethering microtubules into the bipolar configuration of the mitotic apparatus (Merdes et al., 2000; Kisurina-Evgenieva et al, 2004). Although NuMA is not a bona fide constituent of the mitotic centrosome but rather a protein associated with microtubules at the spindle pole, specific splice variants of NuMA have been identified that associate with the centrosome during interphase (Tang et al, 1994).
Identifier: R-HSA-110373
Species: Homo sapiens
Compartment: nucleoplasm
While the single nucleotide replacement pathway appears to facilitate the repair of most damaged bases, an alternative BER pathway is evoked when the structure of the 5'-terminal sugar phosphate is such that it cannot be cleaved through the AP lyase activity of DNA polymerase beta (POLB). Under these circumstances, a short stretch of residues containing the abasic site is excised and replaced (Dianov et al., 1999). Following DNA glycosylase-mediated cleavage of the damaged base, the endonuclease APEX1 is recruited to the site of damage where it cleaves the 5' side of the abasic deoxyribose residue, as in the single nucleotide replacement pathway. However, POLB then synthesizes the first replacement residue without prior cleavage of the 5'-terminal sugar phosphate, hence displacing this entity. Long-patch BER can be completed by continued POLB-mediated DNA strand displacement synthesis in the presence of PARP1 or PARP2, FEN1 and DNA ligase I (LIG1) (Prasad et al. 2001). When the PCNA-containing replication complex is available, as is the case with cells in the S-phase of the cell cycle, DNA strand displacement synthesis is catalyzed by DNA polymerase delta (POLD) or DNA polymerase epsilon (POLE) complexes, in the presence of PCNA, RPA, RFC, APEX1, FEN1 and LIG1 (Klungland and Lindahl 1997, Dianova et al. 2001). In both POLB-dependent and PCNA-dependent DNA displacement synthesis, the displaced DNA strand containing the abasic sugar phosphate creates a flap structure that is recognized and cleaved by the flap endonuclease FEN1. The replacement residues added by POLB or POLD/POLE are then ligated by the DNA ligase I (LIG1) (Klungland and Lindahl, 1997; Matsumoto et al., 1999).

Identifier: R-HSA-73893
Species: Homo sapiens
Compartment: nucleoplasm
In addition to various processes for removing lesions from the DNA, cells have developed specific mechanisms for tolerating unrepaired damage during the replication of the genome. These mechanisms are collectively called DNA damage bypass pathways. The Y family of DNA polymerases plays a key role in DNA damage bypass.

Y family DNA polymerases, REV1, POLH (DNA polymerase eta), POLK (DNA polymerase kappa) and POLI (DNA polymerase iota), as well as the DNA polymerase zeta (POLZ) complex composed of REV3L and MAD2L2, are able to carry out translesion DNA synthesis (TLS) or replicative bypass of damaged bases opposite to template lesions that arrest high fidelity, highly processive replicative DNA polymerase complexes delta (POLD) and epsilon (POLE). REV1, POLH, POLK, POLI and POLZ lack 3'->5' exonuclease activity and exhibit low fidelity and weak processivity. The best established TLS mechanisms are annotated here. TLS details that require substantial experimental clarification have been omitted. For recent and past reviews of this topic, please refer to Lehmann 2000, Friedberg et al. 2001, Zhu and Zhang 2003, Takata and Wood 2009, Ulrich 2011, Saugar et al. 2014.

Identifier: R-HSA-73933
Species: Homo sapiens
Compartment: nucleoplasm
Resolution of AP sites can occur through the single nucleotide replacement pathway or through the multiple nucleotide patch replacement pathway, also known as the long-patch base excision repair (BER). Except for the APEX1-independent resolution of AP sites via single nucleotide base excision repair mediated by NEIL1 or NEIL2 (Wiederhold et al. 2004, Das et al. 2006), single nucleotide and multiple-nucleotide patch replacement pathways are both initiated by APEX1-mediated displacement of DNA glycosylases and cleavage of the damaged DNA strand by APEX1 immediately 5' to the AP site (Wilson et al. 1995, Bennett et al. 1997, Masuda et al. 1998). The BER proceeds via the single nucleotide replacement when the AP (apurinic/apyrimidinic) deoxyribose residue at the 5' end of the APEX1-created single strand break (SSB) (5'dRP) can be removed by the 5'-exonuclease activity of DNA polymerase beta (POLB) (Bennett et al. 1997). POLB fills the created single nucleotide gap by adding a nucleotide complementary to the undamaged DNA strand to the 3' end of the SSB. The SSB is subsequently ligated by DNA ligase III (LIG3) which, in complex with XRCC1, is recruited to the BER site by an XRCC1-mediated interaction with POLB (Kubota et al. 1996). BER proceeds via the multiple-nucleotide patch replacement pathway when the AP residue at the 5' end of the APEX1-created SSB undergoes oxidation-related damage (5'ddRP) and cannot be cleaved by POLB (Klungland and Lindahl 1997). Long-patch BER can be completed by POLB-mediated DNA strand displacement synthesis in the presence of PARP1 or PARP2, FEN1 and DNA ligase I (LIG1) (Prasad et al. 2001). When the PCNA-containing replication complex is available, as is the case with cells in S-phase of the cell cycle, DNA strand displacement synthesis is catalyzed by DNA polymerase delta (POLD) or DNA polymerase epsilon (POLE) complexes, in the presence of PCNA, RPA, RFC, APEX1, FEN1 and LIG1 (Klungland and Lindahl 1997, Dianova et al. 2001). It is likely that the 9-1-1 repair complex composed of HUS1, RAD1 and RAD9 interacts with and coordinates components of BER, but the exact mechanism and timing have not been elucidated (Wang et al. 2004, Smirnova et al. 2005, Guan et al. 2007, Balakrishnan et al. 2009).