bioax途径由Reactome数据库中的“DNA聚合酶delta跨单链缝隙聚合DNA”转化而来。

2.7.7.7

DNA聚合酶通过单链间隙聚合DNA

DNA聚合酶delta在错配修复过程中通过单链间隙合成DNA (Longley et al. 1997, Zhang et al. 2005, Constantin et al. 2005, Prindle and Loeb 2012综述)。RPA刺激DNA聚合酶delta的活性(Dong et al. 1999)。DNA聚合酶delta在合成过程中不会置换链(Randahl et al. 1988)。

作者：2014年3月28日评论:Edelbrock, Michael A, 2014-05-23 编辑:May, B, 2014-03-28

Reactome DB_ID: 5358538

核浆去 0005654 RPA：含有单链缺口的DNA[核质]

RPA：含有单链间隙的DNA

Reactome DB_ID: 68462

RPA异质氧化体[核状]

战heterotrimer

反应数据库ID:68459

UniProt: P35244 RPA3

RPA3

RPA3 REPA3 RPA14 作为异质三聚体复制蛋白A复合物(RPA/RP-A)的一部分，结合并稳定在DNA复制或DNA应激时形成的单链DNA中间产物。它阻止它们的重新退火，同时，招募和激活不同的蛋白质和复合物，参与DNA代谢。因此，它在DNA复制和细胞对DNA损伤的反应中都发挥着重要作用(PubMed:9430682)。在细胞对DNA损伤的反应中，RPA复合物控制DNA修复和DNA损伤检查点的激活。通过募集ATRIP激活ATR激酶，这是DNA损伤反应的主要调节因子(PubMed:24332808)。这是DNA双链断裂修复因子RAD51和RAD52招募到染色质以应对DNA损伤所必需的。也招募到DNA损伤蛋白的位点，如XPA和XPG，参与核苷酸切除修复，是这种DNA修复机制所必需的(PubMed:7697716)。也在基底切除修复(BER)中发挥作用，可能通过与UNG的相互作用(PubMed:9765279)。也将参与复制叉重启的SMARCAL1/HARP招募到DNA损伤的位点。也可能在端粒维持中起作用。 RPA3 has its own single-stranded DNA-binding activity and may be responsible for polarity of the binding of the complex to DNA (PubMed:19010961). As part of the alternative replication protein A complex, aRPA, binds single-stranded DNA and probably plays a role in DNA repair. Compared to the RPA2-containing, canonical RPA complex, may not support chromosomal DNA replication and cell cycle progression through S-phase. The aRPA may not promote efficient priming by DNA polymerase alpha but could support DNA synthesis by polymerase delta in presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange (PubMed:19996105).SUBUNIT Component of the canonical replication protein A complex (RPA), a heterotrimer composed of RPA1, RPA2 and RPA3. Also component of the aRPA, the alternative replication protein A complex, a trimeric complex similar to the replication protein A complex/RPA but where RPA1 and RPA3 are associated with RPA4 instead of RPA2.PTM Ubiquitinated by RFWD3 at stalled replication forks in response to DNA damage: ubiquitination by RFWD3 does not lead to degradation by the proteasome and promotes removal of the RPA complex from stalled replication forks, promoting homologous recombination (PubMed:26474068).SIMILARITY Belongs to the replication factor A protein 3 family. Reactome http://www.reacectome.org. 智人

NCBI分类法 9606 UniProt P35244

链坐标

相同的

121

相同的

反应数据库ID:68457

UniProt: P15927 RPA2

RPA2

RPA2 REPA2 RPA32 RPA34 作为异源三聚体复制蛋白A复合物（RPA/RP-A）的一部分，结合并稳定在DNA复制或DNA应激时形成的单链DNA中间体。它阻止了它们的重新排列，并同时招募和激活了与DNA代谢有关的不同蛋白质和复合物。因此，它在DNA复制和细胞对DNA损伤的反应中起着至关重要的作用。在细胞对DNA损伤的反应中，RPA复合物控制DNA修复和DNA损伤检查点激活。通过招募ATRP激活ATR激酶，ATR激酶是DNA损伤反应的主要调节器。它是DNA双链断裂修复因子RAD51和RAD52招募到染色质以响应DNA损伤所必需的。也招募到DNA损伤蛋白的位点，如XPA和XPG，它们参与核苷酸切除修复，并且是这种DNA修复机制所必需的。在基底切除修复（BER）中也可能通过与UNG的相互作用发挥作用。还招募参与复制叉重新启动的SMARCAL1/HARP到DNA损伤位点。也可能在端粒维持中发挥作用。复制蛋白a复合物（RPA/RP-a）的亚单位成分，一种由RPA1、RPA2和RPA3组成的异源三聚体复合物（PubMed:2406247、PubMed:19116208、PubMed:10449415）。与PRPF19相互作用；PRP19-CDC5L复合物被招募到DNA修复位点，在那里它泛素化复制蛋白A复合物（RPA）（PubMed:24332808）。与SERTAD3交互（PubMed:10982866）。与TIPIN互动（PubMed:17141802，PubMed:17296725）。与永恒互动（PubMed:17141802）。与PPP4R2相互作用；这种相互作用是直接的，依赖于DNA损伤，并介导PP4催化亚单位PPP4C的募集（PubMed:20154705）。与RAD51相互作用（过度磷酸化）（PubMed:20154705）。与SMARCAL1相互作用；这种相互作用是直接的，并介导SMARCAL1的RPA复合体的招募（PubMed:19793861，PubMed:19793862，PubMed:19793863）。与RAD52和XPA相互作用；这些相互作用是直接的，并将RAD52和XPA与RPA复合体相关联（PubMed:7700386，PubMed:8702565，PubMed:17765923，PubMed:11081631）。与FBH1互动（PubMed:23319600）。与ETAA1相互作用；这种互动是直接的，并促进了停滞复制分叉点的ETAA1招募（PubMed:27601467、PubMed:27723720、PubMed:27723717）。与RFWD3交互（PubMed:2154906、PubMed:21558276、PubMed:26474068、PubMed:28575657）。与DDI2（PubMed:29290612）相互作用。诱导对DNA损伤（在蛋白质水平）作出反应时翻译上调。PTM在整个细胞周期中差异磷酸化，在G1-S转换时磷酸化，在有丝分裂后期去磷酸化。在DNA复制和有丝分裂期间，主要通过细胞周期蛋白A-CDK2和细胞周期蛋白B-CDK1在Ser-23和Ser-29处磷酸化。去磷酸化可能需要丝氨酸/苏氨酸蛋白磷酸酶4。Ser-23和Ser-29处的磷酸化是进一步磷酸化的先决条件。在其他残基上变得过度磷酸化，包括Ser-4、Ser-8、Thr-21和Ser-33，以响应DNA损伤。高磷酸化由ATM、ATR和PRKDC介导。主要以次磷酸化形式招募用于DNA修复核病灶，随后在ATR催化下进行高磷酸化。高磷酸化是RAD51招募到染色质和有效DNA修复所必需的。Thr-21的磷酸化取决于RFWD3的存在。由PRPF19诱导的PTM DNA损伤引起的“Lys-63”连接的多泛素化介导ATRIP在DNA损伤和ATR激活位点向RPA复合物募集（PubMed:24332808）。RFWD3在停滞复制分叉处泛素化以应对DNA损伤：RFWD3泛素化不会导致蛋白酶体降解，并促进从停滞复制分叉中去除RPA复合物，促进同源重组（PubMed:26474068）。相似性属于复制因子A蛋白2家族。 UniProt P15927

相同的

270.

相同的

Reactome DB_ID: 68461

UniProt:P27694 RPA1

RPA1

RPA70. RPA1 REPA1 作为异质三聚体复制蛋白A复合物(RPA/RP-A)的一部分，结合并稳定在DNA复制或DNA应激时形成的单链DNA中间产物。它阻止它们重新退火，同时，招募和激活参与DNA代谢的不同蛋白质和复合物(PubMed:27723720, PubMed:27723717)。因此，它在DNA复制和细胞对DNA损伤的反应中都发挥着重要作用(PubMed:9430682)。在细胞对DNA损伤的反应中，RPA复合物控制DNA修复和DNA损伤检查点的激活。通过募集ATRIP激活ATR激酶，这是DNA损伤反应的主要调节因子(PubMed:24332808)。这是为了响应DNA损伤，将DNA双链断裂修复因子RAD51和RAD52招募到染色质中所必需的(PubMed:17765923)。也招募到DNA损伤蛋白的位点，如XPA和XPG，参与核苷酸切除修复，是这种DNA修复机制所必需的(PubMed:7697716)。也可能通过与UNG的相互作用在基底切除修复(BER)中发挥作用(PubMed:9765279)。也将参与复制叉重启的SMARCAL1/HARP招募到DNA损伤的位点。也可能在端粒维持中发挥作用(PubMed:17959650)。 As part of the alternative replication protein A complex, aRPA, binds single-stranded DNA and probably plays a role in DNA repair. Compared to the RPA2-containing, canonical RPA complex, may not support chromosomal DNA replication and cell cycle progression through S-phase. The aRPA may not promote efficient priming by DNA polymerase alpha but could support DNA synthesis by polymerase delta in presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange (PubMed:19996105).SUBUNIT Component of the canonical replication protein A complex (RPA), a heterotrimer composed of RPA1, RPA2 and RPA3 (PubMed:27723720, PubMed:27723717). Also component of the aRPA, the alternative replication protein A complex, a trimeric complex similar to the replication protein A complex/RPA but where RPA1 and RPA3 are associated with RPA4 instead of RPA2 (PubMed:7760808, PubMed:19116208). The DNA-binding activity may reside exclusively on the RPA1 subunit. Interacts with PRPF19; the PRP19-CDC5L complex is recruited to the sites of DNA repair where it ubiquitinates the replication protein A complex (RPA) (PubMed:24332808). Interacts with RIPK1 (PubMed:16135809). Interacts with the polymerase alpha subunit POLA1/p180; this interaction stabilizes the replicative complex and reduces the misincorporation rate of DNA polymerase alpha by acting as a fidelity clamp (PubMed:9214288). Interacts with RAD51 and SENP6 to regulate DNA repair (PubMed:20705237). Interacts with HELB; this interaction promotes HELB recruitment to chromatin following DNA damage (PubMed:22194613, PubMed:26774285). Interacts with PRIMPOL; leading to recruit PRIMPOL on chromatin and stimulate its DNA primase activity (PubMed:24126761, PubMed:25550423, PubMed:28534480). Interacts with XPA; the interaction is direct and associates XPA with the RPA complex (PubMed:7700386, PubMed:9699634, PubMed:10563794). Interacts with ETAA1; the interaction is direct and promotes ETAA1 recruitment at stalled replication forks (PubMed:27601467, PubMed:27723720, PubMed:27723717). Interacts with RPA1; this interaction associates HROB with the RPA complex (By similarity).PTM DNA damage-induced 'Lys-63'-linked polyubiquitination by PRPF19 mediates ATRIP recruitment to the RPA complex at sites of DNA damage and activation of ATR (PubMed:24332808). Ubiquitinated by RFWD3 at stalled replication forks in response to DNA damage: ubiquitination by RFWD3 does not lead to degradation by the proteasome and promotes removal of the RPA complex from stalled replication forks, promoting homologous recombination (PubMed:26474068).PTM Sumoylated on lysine residues Lys-449 and Lys-577, with Lys-449 being the major site. Sumoylation promotes recruitment of RAD51 to the DNA damage foci to initiate DNA repair through homologous recombination. Desumoylated by SENP6.SIMILARITY Belongs to the replication factor A protein 1 family. UniProt P27694

相同的

616

相同的

Reactome数据库ID Release 77 68462 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=68462 Reactome R-HSA-68462

反应稳定标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68462.7

Reactome DB_ID: 5358631

含有单链缺口150-1000 bp的DNA[核质]

DNA含单链间隙150-1000 bp

Reactome数据库ID Release 77 5358538 数据库标识符。使用此URL在反弹中连接到此实例的网页：http：//www.reacontome.org/cgi-bin/eventbrowser?db=gk_current&id=5358538 Reactome r - hsa - 5358538

Reactome稳定的标识符。使用此URL在反弹中连接到此实例的网页：http：//www.reacontome.org/cgi-bin/eventbrowser_st_id?st_id=r-hsa -5358538.1

Reactome DB_ID: 30185

DCTP [Chebi：16311]

dCTP

2'-脱氧胞苷5'-三磷酸盐脱氧胞苷三磷酸脱氧胞苷5'-三磷酸盐车比 16311.

反应数据库ID:29604

DATP [CHEBI：16284]

dATP

2三磷酸脱氧腺苷5 脱氧腺苷三磷酸脱氧腺苷5 '三磷酸车比 16284

Reactome DB_ID: 30187

dTTP (ChEBI: 18077)

dTTP

脱氧胸苷三磷酸 TTP 脱氧胸苷5 '三磷酸车比 18077

反应数据库ID:29892

dGTP (ChEBI: 16497)

dGTP

脱氧鸟苷5'-三磷酸盐 2'-脱氧鸟苷-5'-三磷酸盐脱氧鸟苷三磷酸车比 16497

Reactome DB_ID: 68462

Reactome DB_ID: 5358610

含有单链缺口的DNA（5'磷酸，3'羟基）[核质]

含有单链缺口的DNA（5'磷酸，3'羟基）

PHYSIOL-LEFT-TO-RIGHT

激活

反应数据库ID:68450 DNA聚合酶δ四聚体[核浆]

DNA聚合酶δ四聚体

Reactome DB_ID: 68447

UniProt:Q9HCU8 POLD4

POLD4

波尔兹 POLD4 作为四聚体DNA聚合酶delta复合物(Pol-delta4)的组成部分，在基因组的高保真复制和修复中发挥作用。在这个复合物中，通过调节POLD1聚合酶和校对3'至5'外切酶活性(PubMed:16510448, PubMed:19074196, PubMed:20334433)，提高DNA合成速率并降低保真度。po -delta4通过短瓣途径和缺口翻译系统参与冈崎片段处理(PubMed:24035200)。在DNA复制应激条件下，需要通过断裂诱导复制(break-induced replication, BIR)修复断裂复制叉，这是一种可能诱导高达200kb的基因组片段复制的机制(PubMed:24310611)。参与了带有o6 -甲基鸟嘌呤或基本位点模板的Pol-delta4转译合成(TLS) (PubMed:19074196)。它对DNA损伤的降解是抑制分叉进展和细胞存活所必需的(PubMed:24022480)。四聚体DNA聚合酶delta复合物(Pol-delta4)的亚单位组成，由POLD1/p125, POLD2/p50, POLD3/p66/p68和POLD4/p12组成，POLD1具有DNA聚合酶和3'至5'校对外核酸酶活性(PubMed:16510448, PubMed:17317665, PubMed:22801543)。在这个复合体中，直接与POLD1和POLD2交互(PubMed:12403614, PubMed:16510448)。与PCNA直接相互作用，如POLD1和POLD3;这种相互作用刺激了Pol-delta4聚合酶活性(PubMed:24022480)。 As POLD1 and POLD2, directly interacts with WRNIP1; this interaction stimulates DNA polymerase delta-mediated DNA synthesis, independently of the presence of PCNA. This stimulation may be due predominantly to an increase of initiation frequency and also to increased processivity (PubMed:15670210). Upon genotoxic stress induced by DNA damaging agents or by replication stress, POLD4 is proteolytically degraded and Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3) which has an increased proofreading activity (PubMed:22801543, PubMed:17317665). The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2 (PubMed:12522211).DEVELOPMENTAL STAGE Expression is cell cycle-dependent, with highest levels in G2/M phase and a drastic drop in S phase (PubMed:22801543, PubMed:23913683). This trough may be mediated by DCX(DTL) E3 ubiquitin ligase complex (also called CRL4(CDT2))-mediated proteasomal degradation (PubMed:23913683).INDUCTION In response to DNA damage, genotoxic stress and replication stress, following UV irradiation, ionizing radiation, treatment with methyl methanesulfonate, hydroxyurea, or with aphidicolin, protein expression drops to undetectable levels, due to proteasomal degradation (PubMed:17317665, PubMed:22801543, PubMed:23233665, PubMed:23913683, PubMed:24300032). This down-regulation is ATR-dependent (PubMed:17317665).PTM Ubiquitinated; undergoes 'Lys-48'-linked ubiquitination in response to UV irradiation, leading to proteasomal degradation (PubMed:17317665, PubMed:16934752, PubMed:23233665, PubMed:23913683). This modification is partly mediated by RNF8 and by the DCX(DTL) E3 ubiquitin ligase complex (also called CRL4(CDT2)) (PubMed:23233665, PubMed:24022480). Efficient degradation requires the presence of PCNA and is required for the inhibition of fork progression after DNA damage (PubMed:24022480).SIMILARITY Belongs to the DNA polymerase delta subunit 4 family. UniProt Q9HCU8

相同的

107

相同的

Reactome DB_ID: 68445

UniProt: Q15054 POLD3

POLD3

POLD3 KIAA0039 功能DNA聚合酶delta复合物和DNA聚合酶zeta复合物的辅助成分(PubMed:22801543, PubMed:17317665, PubMed:24449906)。作为三聚体和四聚体DNA聚合酶delta复合物(分别为Pol-delta3和Pol-delta4)的组成部分，在高保真基因组复制中发挥作用，包括滞后链的合成和修复。所需的最佳Pol-delta活性。稳定Pol-delta复合物，并在PCNA刺激Pol-delta中起主要作用(PubMed:10219083, PubMed:10852724, PubMed:11595739, PubMed:16510448, PubMed:24035200)。Pol-delta3和Pol-delta4的特征是不存在或存在POLD4。它们表现出不同的催化活性。最值得注意的是，Pol-delta3比Pol-delta4具有更高的校对活性(PubMed:19074196, PubMed:20334433)。虽然Pol-delta3和Pol-delta4都在体外处理冈崎片段，但Pol-delta3可能更适合完成这一任务，与Pol-delta4相比，它几乎没有链置换活性，并且在遇到5'阻断寡核苷酸时停滞。Pol-delta3空转过程可以避免间隙的形成，同时保持易于结扎的刻痕(PubMed:24035200)。与DNA聚合酶kappa一起，DNA聚合酶delta在紫外线照射后进行大约一半的核苷酸切除修复(NER)合成。 In this context, POLD3, along with PCNA and RFC1-replication factor C complex, is required to recruit POLD1, the catalytic subunit of the polymerase delta complex, to DNA damage sites (PubMed:20227374). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion (PubMed:19074196, PubMed:25628356, PubMed:27185888). Also involved in TLS, as a component of the tetrametric DNA polymerase zeta complex. Along with POLD2, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7 (PubMed:24449906).SUBUNIT Component of both the DNA polymerase delta and DNA polymerase zeta complexes (PubMed:22801543, PubMed:17317665, PubMed:24449906). The tetrameric DNA polymerase delta complex (Pol-delta4), which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and POLD4/p12, with POLD1 bearing DNA polymerase and 3' to 5' proofreading exonuclease activities (PubMed:11328591, PubMed:11595739, PubMed:17317665, PubMed:22801543). Within this complex, directly interacts with POLD2 (PubMed:11328591, PubMed:16510448, PubMed:18818516). Following stress caused by DNA damaging agents or by replication stress, POLD4 is degraded and Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3), which consists of POLD1, POLD2 and POLD3. Pol-delta3 is the major form occurring at S phase replication sites, as well as DNA damage sites (PubMed:11595739, PubMed:17317665, PubMed:22801543, PubMed:23913683). Directly interacts with PCNA, as do POLD1 and POLD4; this interaction stimulates Pol-delta polymerase activity (PubMed:11328591, PubMed:11595739, PubMed:12403614, PubMed:16510448, PubMed:22148433). POLD3 phosphorylation at Ser-458 impairs PCNA binding (PubMed:22148433). Component of the DNA polymerase zeta complex (POLZ), which consists of REV3L, MAD2L2, POLD2 and POLD3, with REV3L bearing DNA polymerase catalytic activity (PubMed:24449906). The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2 (PubMed:12522211).DEVELOPMENTAL STAGE Expression is cell cycle-dependent, with highest levels in G2/M phase and lowest in G1.DOMAIN The PIP-box mediates the interaction with PCNA.PTM Ubiquitinated, but not targeted to the proteasome (PubMed:16934752). Sumoylated (PubMed:16934752, PubMed:25218447). Sumoylation with SUMO3 may be predominant (PubMed:16934752).PTM Phosphorylation at Ser-458 is catalyzed in vitro by PKA. It is thought to decrease the affinity for PCNA and Pol-delta4 processivity (PubMed:22148433). Can also be phosphorylated in vitro by CDK1-cyclin-A complex, as well as CDK2-cyclin-A and CDK2-cyclin-E complexes. PCNA interferes with CDK-cyclin phosphorylation (PubMed:11595739). UniProt Q15054

相同的

466

相同的

Reactome DB_ID: 68443

UniProt:P49005 POLD2

POLD2

POLD2 功能DNA聚合酶delta复合物和DNA聚合酶zeta复合物的辅助成分(PubMed:22801543, PubMed:17317665, PubMed:24449906)。作为三聚体和四聚体DNA聚合酶δ配合物（分别分别在高保真基因组复合物中发挥作用，包括滞后链合成和修复（PubMed：12403614，PubMed：16510448，PubMed：19074196，PubMed：20334433，PubMed：24035200）。Pol-delta3和Pol-delta4的特征是不存在或存在POLD4。它们表现出不同的催化活性。最值得注意的是，Pol-delta3比Pol-delta4具有更高的校对活性(PubMed:19074196, PubMed:20334433)。虽然Pol-delta3和Pol-delta4都在体外处理冈崎片段，但Pol-delta3可能更适合完成这一任务，与Pol-delta4相比，它几乎没有链置换活性，并且在遇到5'阻断寡核苷酸时停滞。Pol-delta3空转过程可以避免间隙的形成，同时保持易于结扎的刻痕(PubMed:24035200)。除了DNA聚合酶Kappa之外，DNA聚合酶DELTA在紫外线照射后进行大约一半的核苷酸切除修复（NER）合成（PUBMED：20227374）。在DNA复制应激条件下，需要通过断裂诱导复制(BIR)修复断裂复制叉(PubMed:24310611)。 Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion. Also involved in TLS as a component of the DNA polymerase zeta complex (PubMed:24449906). Along with POLD3, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7 (PubMed:24449906).SUBUNIT Component of both the DNA polymerase delta and DNA polymerase zeta complexes (PubMed:22801543, PubMed:17317665, PubMed:24449906). Component of the tetrameric DNA polymerase delta complex (Pol-delta4), which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and POLD4/p12, with POLD1 bearing DNA polymerase and 3' to 5' proofreading exonuclease activities (PubMed:22801543, PubMed:17317665). Within Pol-delta4, directly interacts with POLD1, POLD3 and POLD4 (PubMed:11328591, PubMed:16510448). Following stress caused by DNA damaging agents or by replication stress, POLD4 is degraded and Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3), which consists of POLD1, POLD2 and POLD3. Pol-delta3 is the major form occurring at S phase replication sites, as well as DNA damage sites (PubMed:22801543, PubMed:17317665). Also observed as a dimeric complex with POLD2 (Pol-delta2 complex). Pol-delta2 is relatively insensitive to the PCNA stimulation (2-5-fold) compared to Pol-delta4 that is stimulated by over 50-fold (PubMed:12403614). Contrary to the other components of Pol-delta4, does not directly interact with PCNA (PubMed:12403614, PubMed:16510448). As POLD1 and POLD4, directly interacts with WRNIP1; this interaction stimulates DNA polymerase delta-mediated DNA synthesis, independently of the presence of PCNA. This stimulation may be due predominantly to an increase of initiation frequency and also to increased processivity (PubMed:15670210). Directly interacts with POLDIP2 and POLDIP3 (PubMed:12522211). Directly interacts with KCTD13/PDIP1; in the presence of PCNA, this interaction may stimulate DNA polymerase activity (PubMed:11593007). Component of the tetrameric Pol-zeta complex (Pol-zeta4), which consists of REV3L, MAD2L2, POLD2 and POLD3, with REV3L bearing DNA polymerase catalytic activity (PubMed:24449906). Interacts with KCTD10 (By similarity).DEVELOPMENTAL STAGE Expression is cell cycle-dependent, with highest levels in G2/M phase and lowest in S.SIMILARITY Belongs to the DNA polymerase delta/II small subunit family. UniProt P49005

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Reactome DB_ID: 68449

UniProt:P28340 POLD1

POLD1

POLD POLD1 作为三聚体（POL-delta3复合物）和四聚体的DNA聚合酶δ复合物（POL-Delta4的复合物）的催化组分，起着高保真基因组复制了至关重要的作用，包括在后随链合成和修复。既表现出DNA聚合酶和3'至5'外切核酸酶活（PUBMED：16510448，PUBMED：19074196，PUBMED：20334433，PUBMED：24035200，PUBMED：24022480）。需要辅助蛋白POLD2，POLD3和POLD4的全活动的存在。根据不存在（POL-delta3）或POLD4（POL-Delta4的），显示器在催化活性的差异的存在。最值得注意的是，高表达与POL-Delta4的相比，在POL-delta3的背景下校对活动（PUBMED：19074196，考研：20334433）。虽然在体外都POL-delta3和Pol-Delta4的过程冈崎片段，POL-delta3可更好地适合于完成这一任务，显示出近不存在链置换活性的相比POL-Delta4的并与5'-阻挡失速上遭遇寡核苷酸。Pol-delta3空转过程可以避免间隙的形成，同时保持易于结扎的刻痕(PubMed:24035200)。除了DNA聚合酶Kappa之外，DNA聚合酶DELTA在紫外线照射后进行大约一半的核苷酸切除修复（NER）合成（PUBMED：20227374）。下DNA复制胁迫条件下，在POLD3和POLD4的存在下，可催化通过破裂诱导复制（BIR）破复制叉的修复（PUBMED：24310611）。 Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine, 8oxoG or abasic sites (PubMed:19074196, PubMed:24191025).ACTIVITY REGULATION Regulated by alteration of quaternary structure. Exhibits burst rates of DNA synthesis are about 5 times faster in the presence of POLD4 (Pol-delta4 complex) than in its absence (Pol-delta3 complex), while the affinity of the enzyme for its DNA and dNTP substrates appears unchanged. The Pol-delta3 complex is more likely to proofread DNA synthesis because it cleaves single-stranded DNA twice as fast and transfers mismatched DNA from the polymerase to the exonuclease sites 9 times faster compared to the Pol-delta3 complex. Pol-delta3 also extends mismatched primers 3 times more slowly in the absence of POLD4. The conversion of Pol-delta4 into Pol-delta3 is induced by genotoxic stress or by replication stress leading POLD4 degradation (PubMed:19074196, PubMed:20334433). Stimulated in the presence of PCNA (PubMed:11328591, PubMed:12403614, PubMed:12522211, PubMed:16510448, PubMed:24022480, PubMed:24939902). This stimulation is further increased in the presence of KCTD13/PDIP1, most probably via direct interaction between KCTD13 and POLD2 (By similarity).SUBUNIT Component of the tetrameric DNA polymerase delta complex (Pol-delta4), which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and POLD4/p12, with POLD1 bearing both DNA polymerase and 3' to 5' proofreading exonuclease activities (PubMed:11595739, PubMed:12522211, PubMed:17317665, PubMed:22801543). Within Pol-delta4, directly interacts with POLD2 and POLD4 (PubMed:11328591, PubMed:12403614, PubMed:16510448). Following genotoxic stress by DNA-damaging agents, such as ultraviolet light and methyl methanesulfonate, or by replication stress induced by treatment with hydroxyurea or aphidicolin, Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3) by POLD4 degradation. Pol-delta3 is the major form at S phase replication sites and DNA damage sites (PubMed:22801543, PubMed:17317665). POLD1 displays different catalytic properties depending upon the complex it is found in (PubMed:17317665). It exhibits higher proofreading activity and fidelity than Pol-delta4, making it particularly well suited to respond to DNA damage (PubMed:19074196, PubMed:20334433). Directly interacts with PCNA, as do POLD3 and POLD4; this interaction stimulates Pol-delta4 polymerase activity (PubMed:11328591, PubMed:12403614, PubMed:12522211, PubMed:16510448, PubMed:24022480, PubMed:24939902). As POLD2 and POLD4, directly interacts with WRNIP1; this interaction stimulates DNA polymerase delta-mediated DNA synthesis, independently of the presence of PCNA. This stimulation may be due predominantly to an increase of initiation frequency and also to increased processivity (PubMed:15670210). Also observed as a dimeric complex with POLD2 (Pol-delta2 complex). Pol-delta2 is relatively insensitive to the PCNA stimulation (2-5-fold) compared to Pol-delta4 that is stimulated by over 50-fold (PubMed:12403614). The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2 (PubMed:12522211). Interacts with CIAO1 (PubMed:23891004). Interacts with POLDIP2 (PubMed:24191025).TISSUE SPECIFICITY Widely expressed, with high levels of expression in heart and lung.DEVELOPMENTAL STAGE Expression is cell cycle-dependent, with highest levels in G2/M phase and lowest in G1.INDUCTION Up-regulated by serum stimulation.DOMAIN The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes.SIMILARITY Belongs to the DNA polymerase type-B family. UniProt P28340

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Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68450.1 去 0003887.

GO分子函数

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反应稳定标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5358579.1 16188885. Pubmed 2005 人类错配修复：缺口定向双向反应的重建康宁，尼科塔赞提耶夫，列奥尼德卡德罗夫,法 Modrich,保罗比奥。化学。280:39752-61 16143102 Pubmed 2005 在纯化系统中重构5'-定向人体不匹配修复张Yanbin 元,奉化普雷斯内尔，史蒂文R 田，凯利高,阴 Tomkinson，Alan E 顾,Liya 李Guo-Min 细胞122:693 - 705 9099749 Pubmed 1997 DNA聚合酶δ是体外人类错配修复所必需的 Longley，M J 皮尔斯，一个j Modrich P 生物。化学。272：10917-21 9882630 Pubmed 1999年人复制蛋白A中锌指基序的体外分析董，J 公园，j s 李，SH 物化学。j . 337:311-7 2842325. Pubmed 1988 纯化HeLa-DNA聚合酶和核酸外切酶的DNA修复反应 Randahl H 艾略特,G C 林恩，S 生物。化学263:12228-34 23065663 Pubmed 2012 DNA复制和基因组维持中的DNA聚合酶delta 普林德尔，马克J 勒布，劳伦斯A 环绕。摩尔,诱变剂。53:666 - 82