scholarly journals Translesion Synthesis across Abasic Lesions by Human B-Family and Y-Family DNA Polymerases α, δ, η, ι, κ, and REV1

2010 ◽  
Vol 404 (1) ◽  
pp. 34-44 ◽  
Author(s):  
Jeong-Yun Choi ◽  
Seonhee Lim ◽  
Eun-Jin Kim ◽  
Ara Jo ◽  
F. Peter Guengerich
Keyword(s):  
Dna Polymerases ◽  
Translesion Synthesis ◽  
Y Family

scholarly journals Implications of inhibition of Rev1 interaction with Y family DNA polymerases for cisplatin chemotherapy

2021 ◽  
Author(s):  
Jung-Hoon Yoon ◽  
Robert E. Johnson ◽  
Louise Prakash ◽  
Satya Prakash
Keyword(s):  
Adverse Effects ◽  
Cancer Cells ◽  
Dna Polymerases ◽  
Translesion Synthesis ◽  
Dna Adduct ◽  
Secondary Malignancies ◽  
Normal Cells ◽  
Cross Links ◽  
Y Family

Chemotherapy with cisplatin becomes limiting due to toxicity and secondary malignancies. In principle, therapeutics could be improved by targeting translesion synthesis (TLS) polymerases (Pols) that promote replication through intrastrand cross-links, the major cisplatin-induced DNA adduct. However, to specifically target malignancies with minimal adverse effects on normal cells, a good understanding of TLS mechanisms in normal versus cancer cells is paramount. We show that in normal cells, TLS through cisplatin intrastrand cross-links is promoted by Polη- or Polι-dependent pathways, both of which require Rev1 as a scaffolding component. In contrast, cancer cells require Rev1-Polζ. Our findings that a recently identified Rev1 inhibitor, JH-RE-06, purported to specifically disrupt Rev1 interaction with Polζ to block TLS through cisplatin adducts in cancer cells, abrogates Rev1's ability to function with Y family Pols as well, implying that by inactivating Rev1-dependent TLS in normal cells, this inhibitor will exacerbate the toxicity and tumorigenicity of chemotherapeutics with cisplatin.

scholarly journals Mechanism of Translesion Synthesis Past an Equine Estrogen-DNA Adduct by Y-Family DNA Polymerases

2007 ◽  
Vol 371 (5) ◽  
pp. 1151-1162 ◽  
Author(s):  
Manabu Yasui ◽  
Naomi Suzuki ◽  
Xiaoping Liu ◽  
Yoshinori Okamoto ◽  
Sung Yeon Kim ◽  
...  
Keyword(s):  
Dna Polymerases ◽  
Translesion Synthesis ◽  
Dna Adduct ◽  
Y Family

scholarly journals Translesion synthesis across the (6-4) photoproduct and its Dewar valence isomer by the Y-family and engineered DNA polymerases

2008 ◽  
Vol 52 (1) ◽  
pp. 339-340 ◽  
Author(s):  
J. Yamamoto ◽  
D. Loakes ◽  
C. Masutani ◽  
S. Simmyo ◽  
K. Urabe ◽  
...  
Keyword(s):  
Dna Polymerases ◽  
Translesion Synthesis ◽  
Y Family

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 Translesion synthesis DNA polymerases promote error-free replication through the minor-groove DNA adduct 3-deaza-3-methyladenine

2017 ◽  
Vol 292 (45) ◽  
pp. 18682-18688 ◽  
Author(s):  
Jung-Hoon Yoon ◽  
Jayati Roy Choudhury ◽  
Jeseong Park ◽  
Satya Prakash ◽  
Louise Prakash
Keyword(s):  
Dna Polymerases ◽  
Translesion Synthesis ◽  
Minor Groove ◽  
Dna Adduct

Frameshifts and deletions during in vitro translesion synthesis past Pt–DNA adducts by DNA polymerases β and η

DNA Repair ◽  
2002 ◽  
Vol 1 (12) ◽  
pp. 1003-1016 ◽  
Author(s):  
Ekaterina Bassett ◽  
Alexandra Vaisman ◽  
Kristen A. Tropea ◽  
Chad M. McCall ◽  
Chikahide Masutani ◽  
...  
Keyword(s):  
Dna Adducts ◽  
Dna Polymerases ◽  
Translesion Synthesis

Translesion Synthesis past Equine Estrogen-Derived 2‘-Deoxycytidine DNA Adducts by Human DNA Polymerases η and κ†

Biochemistry ◽  
2004 ◽  
Vol 43 (35) ◽  
pp. 11312-11320 ◽  
Author(s):  
Naomi Suzuki ◽  
Manabu Yasui ◽  
Y. R. Santosh Laxmi ◽  
Haruo Ohmori ◽  
Fumio Hanaoka ◽  
...  
Keyword(s):  
Dna Adducts ◽  
Dna Polymerases ◽  
Translesion Synthesis ◽  
Human Dna

scholarly journals Diverse roles of RAD18 and Y-family DNA polymerases in tumorigenesis

Cell Cycle ◽  
2018 ◽  
Vol 17 (7) ◽  
pp. 833-843 ◽  
Author(s):  
Yang Yang ◽  
Yanzhe Gao ◽  
Anastasia Zlatanou ◽  
Satoshi Tateishi ◽  
Vyacheslav Yurchenko ◽  
...  
Keyword(s):  
Dna Polymerases ◽  
Y Family

Tissue methylation and demethylation influence translesion synthesis DNA polymerases (TLS) contributing to the genesis of chromosomal abnormalities in myelodysplastic syndrome

2020 ◽  
pp. jclinpath-2020-207131
Author(s):  
Gabrielle Melo Cavalcante ◽  
Daniela Paula Borges ◽  
Roberta Taiane Germano de Oliveira ◽  
Cristiana Libardi Miranda Furtado ◽  
Ana Paula Negreiros Nunes Alves ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Chromosomal Abnormalities ◽  
Dna Polymerases ◽  
Translesion Synthesis ◽  
Normal Karyotype ◽  
Dna Demethylation ◽  
Repair System ◽  
Low Expression

AimsDNA methylation has its distribution influenced by DNA demethylation processes with the catalytic conversion of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Myelodysplastic syndrome (MDS) has been associated with epigenetic dysregulation of genes related to DNA repair system, chronic immune response and cell cycle.MethodsWe evaluated the tissue DNA methylation/hydroxymethylation in bone marrow trephine biopsies of 73 patients with MDS, trying to correlate with the mRNA expression of 21 genes (POLH, POLL, REV3L, POLN, POLQ, POLI, POLK, IRF-1, IRF-2, IRF-3, IRF-4, IRF-5, IRF6, IRF-7, IRF-8,IRF-9, MAD2, CDC20, AURKA, AURKB and TPX2).ResultsThe M-score (5mC) was significantly higher in patients with chromosomal abnormalities than patients with normal karyotype (95% CI –27.127779 to –2.368020; p=0.022). We observed a higher 5mC/5hmC ratio in patients classified as high-risk subtypes compared with low-risk subtypes (95% CI –72.922115 to –1.855662; p=0.040) as well as patients with hypercellular bone marrow compared with patients with normocellular/hypocellular bone marrow (95% CI –69.189259 to –0.511828; p=0.047) and with the presence of dyserythropoiesis (95% CI 17.077703 to 51.331388; p=0.001). DNA pols with translesion activity are significantly influenced by methylation. As 5mC immunoexpression increases, the expressions of POLH (r=−0.816; r2 =0.665; p=0.000), POLQ (r=−0.790; r2=0.624; p=0.001), PCNA (r=−0.635; r2=0.403; p=0.020), POLK (r=−0.633; r2=0.400; p=0.036 and REV1 (r=−0.578; r2=0.334; p=0.049) decrease.ConclusionsOur results confirm that there is an imbalance in the DNA methylation in MDS, influencing the development of chromosomal abnormalities which may be associated with the low expression of DNA polymerases with translesion synthesis polymerases activity.

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