Polymerization Past the N2-Isopropylguanine and the N6-Isopropyladenine DNA Lesions with the Translesion Synthesis DNA Polymerases η and ι and the Replicative DNA Polymerase α†

2005 ◽  
Vol 18 (9) ◽  
pp. 1451-1461 ◽  
Author(s):  
Fred W. Perrino ◽  
Scott Harvey ◽  
Patrick Blans ◽  
Stacy Gelhaus ◽  
William R. LaCourse ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Dna Polymerases ◽  
Translesion Synthesis ◽  
Dna Lesions ◽  
Dna Polymerase Α

scholarly journals Rev1 promotes replication through UV lesions in conjunction with DNA polymerases η, ι, and κ but not DNA polymerase ζ

2015 ◽  
Vol 29 (24) ◽  
pp. 2588-2602 ◽  
Author(s):  
Jung-Hoon Yoon ◽  
Jeseong Park ◽  
Juan Conde ◽  
Maki Wakamiya ◽  
Louise Prakash ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Crucial Role ◽  
Genome Stability ◽  
Dna Polymerases ◽  
Translesion Synthesis ◽  
Dna Lesions ◽  
Human Cells ◽  
Uv Lesions ◽  
Human And Mouse

Translesion synthesis (TLS) DNA polymerases (Pols) promote replication through DNA lesions; however, little is known about the protein factors that affect their function in human cells. In yeast, Rev1 plays a noncatalytic role as an indispensable component of Polζ, and Polζ together with Rev1 mediates a highly mutagenic mode of TLS. However, how Rev1 functions in TLS and mutagenesis in human cells has remained unclear. Here we determined the role of Rev1 in TLS opposite UV lesions in human and mouse fibroblasts and showed that Rev1 is indispensable for TLS mediated by Polη, Polι, and Polκ but is not required for TLS by Polζ. In contrast to its role in mutagenic TLS in yeast, Rev1 promotes predominantly error-free TLS opposite UV lesions in humans. The identification of Rev1 as an indispensable scaffolding component for Polη, Polι, and Polκ, which function in TLS in highly specialized ways opposite a diverse array of DNA lesions and act in a predominantly error-free manner, implicates a crucial role for Rev1 in the maintenance of genome stability in humans.

scholarly journals Role of Translesion Synthesis DNA Polymerases in DNA Replication in the Presence of a Weak DNA Polymerase δ in Saccharomyces cerevisiae

2018 ◽  
Vol 8 (2) ◽  
pp. 754-754
Author(s):  
Likui Zhang ◽  
Yanchao Huang ◽  
Xinyuan Zhu ◽  
Yuxiao Wang ◽  
Haoqiang Shi ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Replication ◽  
Dna Polymerase ◽  
Dna Polymerases ◽  
Translesion Synthesis ◽  
Dna Polymerase Δ

scholarly journals Human DNA Polymerase ι Promotes Replication through a Ring-Closed Minor-Groove Adduct That Adopts a syn Conformation in DNA

2005 ◽  
Vol 25 (19) ◽  
pp. 8748-8754 ◽  
Author(s):  
William T. Wolfle ◽  
Robert E. Johnson ◽  
Irina G. Minko ◽  
R. Stephen Lloyd ◽  
Satya Prakash ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Dna Polymerases ◽  
Minor Groove ◽  
Dna Lesions ◽  
Unsaturated Aldehyde ◽  
Cyclic Form ◽  
Human Dna ◽  
A Minor ◽  
Dna Polymerase Ι

ABSTRACT Acrolein, an α,β-unsaturated aldehyde, is generated in vivo as the end product of lipid peroxidation and from oxidation of polyamines. The reaction of acrolein with the N 2 group of guanine in DNA leads to the formation of a cyclic adduct, γ-hydroxy-1,N 2-propano-2′-deoxyguanosine (γ-HOPdG). Previously, we have shown that proficient replication through the γ-HOPdG adduct can be mediated by the sequential action of human DNA polymerases (Pols) ι and κ, in which Polι incorporates either pyrimidine opposite γ-HOPdG, but Polκ extends only from the cytosine. Since γ-HOPdG can adopt either a ring-closed cyclic form or a ring-opened form in DNA, to better understand the mechanisms that Pols ι and κ employ to promote replication through this lesion, we have examined the ability of these polymerases to replicate through the structural analogs of γ-HOPdG that are permanently either ring closed or ring opened. Our studies with these model adducts show that whereas the ring-opened form of γ-HOPdG is not inhibitory to synthesis by human Pols η, ι, or κ, only Polι is able to incorporate nucleotides opposite the ring-closed form, which is known to adopt a syn conformation in DNA. From these studies, we infer that (i) Pols η, ι, and κ have the ability to proficiently replicate through minor-groove DNA lesions that do not perturb the Watson-Crick hydrogen bonding of the template base with the incoming nucleotide, and (ii) Polι can accommodate a minor-groove-adducted template purine which adopts a syn conformation in DNA and forms a Hoogsteen base pair with the incoming nucleotide.

scholarly journals Role of Translesion Synthesis DNA Polymerases in DNA Replication in the Presence of a Weak DNA Polymerase δ in Saccharomyces cerevisiae

2017 ◽  
Vol 8 (2) ◽  
pp. 754-754
Author(s):  
Likui Zhang ◽  
Yanchao Huang ◽  
Xinyuan Zhu ◽  
Yuxiao Wang ◽  
Haoqiang Shi ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Replication ◽  
Dna Polymerase ◽  
Dna Polymerases ◽  
Translesion Synthesis ◽  
Dna Polymerase Δ

Reduced Repair of X-Ray-Induced DNA Lesions in Cells without Functioning DNA Polymerase α

1985 ◽  
Vol 102 (1) ◽  
pp. 71 ◽  
Author(s):  
Ulf Lönn ◽  
Sigrid Lönn ◽  
Ulf Lonn ◽  
Sigrid Lonn
Keyword(s):  
Dna Polymerase ◽  
Dna Lesions ◽  
X Ray ◽  
Dna Polymerase Α ◽  
In Cells

scholarly journals PCNA Mono-Ubiquitination and Activation of Translesion DNA Polymerases by DNA Polymerase α

2009 ◽  
Vol 146 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Motoshi Suzuki ◽  
Atsuko Niimi ◽  
Siripan Limsirichaikul ◽  
Shuta Tomida ◽  
Qin Miao Huang ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Dna Polymerases ◽  
Dna Polymerase Α ◽  
Translesion Dna

scholarly journals The N-Terminal Noncatalytic Region of Xenopus RecQ4 Is Required for Chromatin Binding of DNA Polymerase α in the Initiation of DNA Replication

2006 ◽  
Vol 26 (13) ◽  
pp. 4843-4852 ◽  
Author(s):  
Kumiko Matsuno ◽  
Maya Kumano ◽  
Yumiko Kubota ◽  
Yoshitami Hashimoto ◽  
Haruhiko Takisawa
Keyword(s):  
Dna Replication ◽  
Dna Polymerase ◽  
Sequence Similarity ◽  
Dna Polymerases ◽  
Helicase Domain ◽  
Chromatin Binding ◽  
Replication Machinery ◽  
Dna Polymerase Α ◽  
Initiation Of Dna Replication ◽  
Replication Activity

ABSTRACT Recruitment of DNA polymerases onto replication origins is a crucial step in the assembly of eukaryotic replication machinery. A previous study in budding yeast suggests that Dpb11 controls the recruitment of DNA polymerases α and ε onto the origins. Sld2 is an essential replication protein that interacts with Dpb11, but no metazoan homolog has yet been identified. We isolated Xenopus RecQ4 as a candidate Sld2 homolog. RecQ4 is a member of the metazoan RecQ helicase family, and its N-terminal region shows sequence similarity with Sld2. In Xenopus egg extracts, RecQ4 is essential for the initiation of DNA replication, in particular for chromatin binding of DNA polymerase α. An N-terminal fragment of RecQ4 devoid of the helicase domain could rescue the replication activity of RecQ4-depleted extracts, and antibody against the fragment inhibited DNA replication and chromatin binding of the polymerase. Further, N-terminal fragments of RecQ4 physically interacted with Cut5, a Xenopus homolog of Dpb11, and their ability to bind to Cut5 closely correlated with their ability to rescue the replication activity of the depleted extracts. Our data suggest that RecQ4 performs an essential role in the assembly of replication machinery through interaction with Cut5 in vertebrates.

scholarly journals TENT4A Non-Canonical Poly(A) Polymerase Regulates DNA-Damage Tolerance via Multiple Pathways That Are Mutated in Endometrial Cancer

2021 ◽  
Vol 22 (13) ◽  
pp. 6957
Author(s):  
Umakanta Swain ◽  
Gilgi Friedlander ◽  
Urmila Sehrawat ◽  
Avital Sarusi-Portuguez ◽  
Ron Rotkopf ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Dna Polymerase ◽  
Mrna Stability ◽  
Antisense Rna ◽  
Bioinformatics Analysis ◽  
Dna Polymerases ◽  
Dna Lesions ◽  
Dna Damage Tolerance ◽  
Translesion Dna Synthesis ◽  
Cancer Genomes

TENT4A (PAPD7) is a non-canonical poly(A) polymerase, of which little is known. Here, we show that TENT4A regulates multiple biological pathways and focuses on its multilayer regulation of translesion DNA synthesis (TLS), in which error-prone DNA polymerases bypass unrepaired DNA lesions. We show that TENT4A regulates mRNA stability and/or translation of DNA polymerase h and RAD18 E3 ligase, which guides the polymerase to replication stalling sites and monoubiquitinates PCNA, thereby enabling recruitment of error-prone DNA polymerases to damaged DNA sites. Remarkably, in addition to the effect on RAD18 mRNA stability via controlling its poly(A) tail, TENT4A indirectly regulates RAD18 via the tumor suppressor CYLD and via the long non-coding antisense RNA PAXIP1-AS2, which had no known function. Knocking down the expression of TENT4A or CYLD, or overexpression of PAXIP1-AS2 led each to reduced amounts of the RAD18 protein and DNA polymerase h, leading to reduced TLS, highlighting PAXIP1-AS2 as a new TLS regulator. Bioinformatics analysis revealed that TLS error-prone DNA polymerase genes and their TENT4A-related regulators are frequently mutated in endometrial cancer genomes, suggesting that TLS is dysregulated in this cancer.

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