PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication.
PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication.
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DOI：
10.1016/j.molcel.2013.10.035
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发表时间：
2013-11-21
期刊：
影响因子：
16
通讯作者：
Doherty, Aidan J.
中科院分区：
文献类型：
--
作者：
Bianchi, Julie;Rudd, Sean G.;Jozwiakowski, Stanislaw K.;Bailey, Laura J.;Soura, Violetta;Taylor, Elaine;Stevanovic, Irena;Green, Andrew J.;Stracker, Travis H.;Lindsay, Howard D.;Doherty, Aidan J.
DNA损伤可以阻止DNA复制机制，导致基因组不稳定。因此，在没有原始DNA模板的情况下，存在许多机制来完成基因组复制，但对所涉及的酶的鉴定仍然不完整。在这里，我们建立了引物聚合酶（PrimPol; CCDC 111），真核细胞中的古-真核引物酶（AEP），参与染色体DNA复制。PrimPol是紫外线（UV）光损伤DNA模板上复制叉进展所必需的，可能是由其催化这些病变的跨病变合成（TLS）的能力介导的。该PrimPol UV损伤旁路途径与Pol η依赖性途径不上位，因此保护着色性干皮病变体（XP-V）患者细胞免受UV诱导的细胞毒性。此外，我们还确定PrimPol也是在未受干扰的S期期间有效复制叉进展所需的。这些和其他发现表明PrimPol是真核细胞中复制叉进展的重要参与者。PrimPol是一种催化绕过UV和氧化损伤的DNA引物酶聚合酶PrimPol在与Pol η非上位性的UV损伤耐受途径中运行PrimPol无效细胞在分叉进展中有缺陷，特别是在UV处理后PrimPol的缺失导致有丝分裂染色体断裂增加
DNA damage can stall the DNA replication machinery, leading to genomic instability. Thus, numerous mechanisms exist to complete genome duplication in the absence of a pristine DNA template, but identification of the enzymes involved remains incomplete. Here, we establish that Primase-Polymerase (PrimPol; CCDC111), an archaeal-eukaryotic primase (AEP) in eukaryotic cells, is involved in chromosomal DNA replication. PrimPol is required for replication fork progression on ultraviolet (UV) light-damaged DNA templates, possibly mediated by its ability to catalyze translesion synthesis (TLS) of these lesions. This PrimPol UV lesion bypass pathway is not epistatic with the Pol η-dependent pathway and, as a consequence, protects xeroderma pigmentosum variant (XP-V) patient cells from UV-induced cytotoxicity. In addition, we establish that PrimPol is also required for efficient replication fork progression during an unperturbed S phase. These and other findings indicate that PrimPol is an important player in replication fork progression in eukaryotic cells. PrimPol is a DNA primase-polymerase catalyzing bypass of UV and oxidative lesions PrimPol operates in a UV lesion tolerance pathway that is non-epistatic with Pol η PrimPol null cells are defective in fork progression, particularly after UV treatment Loss of PrimPol leads to increased mitotic chromosomal breaks
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影响因子：
11.4
作者：
Betous, Remy;Pillaire, Marie-Jeanne;Pierini, Laura;van der Laan, Siem;Recolin, Benedicte;Ohl-Seguy, Emma;Guo, Caixia;Niimi, Naoko;Gruz, Petr;Nohmi, Takehiko;Friedberg, Errol;Cazaux, Christophe;Maiorano, Domenico;Hoffmann, Jean-Sebastien
通讯作者：
Hoffmann, Jean-Sebastien
影响因子：
56.9
作者：
Della, M;Palmbos, PL;Doherty, AJ
通讯作者：
Doherty, AJ
DOI：
10.1083/jcb.123.6.1321
发表时间：
1993-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kubota Y;Takisawa H
通讯作者：
Takisawa H
影响因子：
7.8
作者：
MURRAY, MT;KROHNE, G;FRANKE, WW
通讯作者：
FRANKE, WW
影响因子：
56.9
作者：
Michael, WM;Ott, R;Newport, J
通讯作者：
Newport, J