country

Change Language

EN - English
FR - Français
DE - Deutsch
ES - Español
JA - 日本語
KO - 한국어

Country or Region:

United States

Product Name	Size / Unit Price	Qty

Total: USD 0.00 Checkout

DNA-directed primase/polymerase protein

Definition:

DNA primase and DNA polymerase required to tolerate replication-stalling lesions by bypassing them. Required to facilitate mitochondrial and nuclear replication fork progression by initiating de novo DNA synthesis using dNTPs and acting as an error-prone DNA polymerase able to bypass certain DNA lesions. Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA. Provides different translesion synthesis alternatives when DNA replication is stalled: able to synthesize DNA primers downstream of lesions, such as ultraviolet (UV) lesions, R-loops and G-quadruplexes, to allow DNA replication to continue. Can also realign primers ahead of 'unreadable lesions' such as abasic sites and 6-4 photoproduct (6-4 pyrimidine-pyrimidinone), thereby skipping the lesion. Also able to incorporate nucleotides opposite DNA lesions such as 8oxoG, like a regular translesion synthesis DNA polymerase. Also required for reinitiating stalled forks after UV damage during nuclear DNA replication. Required for mitochondrial DNA (mtDNA) synthesis and replication, by reinitiating synthesis after UV damage or in the presence of chain-terminating nucleotides. Prevents APOBEC family-mediated DNA mutagenesis by repriming downstream of abasic site to prohibit error-prone translesion synthesis (By similarity). Has non-overlapping function with POLH. In addition to its role in DNA damage response, also required to maintain efficient nuclear and mitochondrial DNA replication in unperturbed cells.; Involved in adaptive response to cisplatin, a chemotherapeutic that causes reversal of replication forks, in cancer cells: reinitiates DNA synthesis past DNA lesions in BRCA1-deficient cancer cells treated with cisplatin via its de novo priming activity. Repriming rescues fork degradation while leading to accumulation of internal ssDNA gaps behind the forks. ATR regulates adaptive response to cisplatin.

References:

[1]. Thomas A Guilliam, et al. Molecular basis for PrimPol recruitment to replication forks by RPA. Nat Commun. 2017 May 23;8:15222. [Content Brief]

[2]. Sara García-Gómez, et al. PrimPol, an archaic primase/polymerase operating in human cells. Mol Cell. 2013 Nov 21;52(4):541-53. [Content Brief]

[3]. Saša Šviković, et al. R-loop formation during S phase is restricted by PrimPol-mediated repriming. EMBO J. 2019 Feb 1;38(3):e99793. [Content Brief]

[4]. Julie Bianchi, et al. PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication. Mol Cell. 2013 Nov 21;52(4):566-73. [Content Brief]

[5]. Wenyan Xu, et al. Divalent Cations Alter the Rate-Limiting Step of PrimPol-Catalyzed DNA Elongation. J Mol Biol. 2019 Feb 15;431(4):673-686. [Content Brief]

[6]. Silvana Mourón, et al. Repriming of DNA synthesis at stalled replication forks by human PrimPol. Nat Struct Mol Biol. 2013 Dec;20(12):1383-9. [Content Brief]

[7]. Davide Schiavone, et al. PrimPol Is Required for Replicative Tolerance of G Quadruplexes in Vertebrate Cells. Mol Cell. 2016 Jan 7;61(1):161-9. [Content Brief]

[8]. Li Wan, et al. hPrimpol1/CCDC111 is a human DNA primase-polymerase required for the maintenance of genome integrity. EMBO Rep. 2013 Dec;14(12):1104-12. [Content Brief]

[9]. Benjamin A Keen, et al. Human PrimPol mutation associated with high myopia has a DNA replication defect. Nucleic Acids Res. 2014 Oct 29;42(19):12102-11. [Content Brief]

[10]. Benjamin A Keen, et al. Molecular dissection of the domain architecture and catalytic activities of human PrimPol. Nucleic Acids Res. 2014 May;42(9):5830-45. [Content Brief]

[11]. Annabel Quinet, et al. PRIMPOL-Mediated Adaptive Response Suppresses Replication Fork Reversal in BRCA-Deficient Cells. Mol Cell. 2020 Feb 6;77(3):461-474.e9. [Content Brief]

[12]. María I Martínez-Jiménez, et al. Alternative solutions and new scenarios for translesion DNA synthesis by human PrimPol. DNA Repair (Amst). 2015 May;29:127-38. [Content Brief]

[13]. Thomas A Guilliam, et al. Human PrimPol is a highly error-prone polymerase regulated by single-stranded DNA binding proteins. Nucleic Acids Res. 2015 Jan;43(2):1056-68. [Content Brief]

[14]. Patricia A Calvo, et al. The invariant glutamate of human PrimPol DxE motif is critical for its Mn2+-dependent distinctive activities. DNA Repair (Amst). 2019 May;77:65-75. [Content Brief]

[15]. Laura J Bailey, et al. PrimPol is required for the maintenance of efficient nuclear and mitochondrial DNA replication in human cells. Nucleic Acids Res. 2019 May 7;47(8):4026-4038. [Content Brief]

[16]. E John Tokarsky, et al. Significant impact of divalent metal ions on the fidelity, sugar selectivity, and drug incorporation efficiency of human PrimPol. DNA Repair (Amst). 2017 Jan;49:51-59. [Content Brief]

[17]. María I Martínez-Jiménez, et al. The Zn-finger domain of human PrimPol is required to stabilize the initiating nucleotide during DNA priming. Nucleic Acids Res. 2018 May 4;46(8):4138-4151. [Content Brief]

[18]. Maroof K Zafar, et al. Kinetic analysis of human PrimPol DNA polymerase activity reveals a generally error-prone enzyme capable of accurately bypassing 7,8-dihydro-8-oxo-2'-deoxyguanosine. Biochemistry. 2014 Oct 21;53(41):6584-94. [Content Brief]

Biomedical Dictionary

The Biomedical Dictionary is a comprehensive and professional collection of biological academic terms and subject datas. All explanations are supported by authoritative books or high impact factor literatures, and you can acquire accurate explanations of the biomedical terms you want to know.

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z #