scholarly journals Mutational Specificity of γ-Radiation-Induced Guanine−Thymine and Thymine−Guanine Intrastrand Cross-Links in Mammalian Cells and Translesion Synthesis Past the Guanine−Thymine Lesion by Human DNA Polymerase η†

Biochemistry ◽  
2008 ◽  
Vol 47 (31) ◽  
pp. 8070-8079 ◽  
Author(s):  
Laureen C. Colis ◽  
Paromita Raychaudhury ◽  
Ashis K. Basu
Keyword(s):  
Dna Polymerase ◽  
Mammalian Cells ◽  
Translesion Synthesis ◽  
Γ Radiation ◽  
Human Dna ◽  
Mutational Specificity ◽  
Radiation Induced ◽  
Cross Links

scholarly journals Replication Past the -Radiation-Induced Guanine-Thymine Cross-Link G[8,5-Me]T by Human and Yeast DNA Polymerase

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Paromita Raychaudhury ◽  
Ashis K. Basu
Keyword(s):  
Dna Polymerase ◽  
Mammalian Cells ◽  
Translesion Synthesis ◽  
Kidney Cells ◽  
Equal Frequency ◽  
Cross Link ◽  
Dominant Mutation ◽  
Human Embryonic Kidney Cells ◽  
Radiation Induced

-Radiation-induced intrastrand guanine-thymine cross-link, G[8,5-Me]T, hinders replicationin vitroand is mutagenic in mammalian cells. Herein we reportin vitrotranslesion synthesis of G[8,5-Me]T by human and yeast DNA polymerase (hPol and yPol ). dAMP misincorporation opposite the cross-linked G by yPol was preferred over correct incorporation of dCMP, but further extension was 100-fold less efficient for :A compared to :C. For hPol , both incorporation and extension were more efficient with the correct nucleotides. To evaluate translesion synthesis in the presence of all four dNTPs, we have developed a plasmid-based DNA sequencing assay, which showed that yPol was more error-prone. Mutational frequencies of yPol and hPol were 36% and 14%, respectively. Targeted was the dominant mutation by both DNA polymerases. But yPol induced targeted in 23% frequency relative to 4% by hPol . For yPol , targeted and constituted 83% of the mutations. By contrast, with hPol , semi-targeted mutations (7.2%), that is, mutations at bases near the lesion, occurred at equal frequency as the targeted mutations (6.9%). The kind of mutations detected with hPol showed significant similarities with the mutational spectrum of G[8,5-Me]T in human embryonic kidney cells.

scholarly journals DNA polymerase ζ in DNA replication and repair

2019 ◽  
Vol 47 (16) ◽  
pp. 8348-8361 ◽  
Author(s):  
Sara K Martin ◽  
Richard D Wood
Keyword(s):  
Dna Replication ◽  
Dna Polymerase ◽  
Dna Sequences ◽  
Mammalian Cells ◽  
Translesion Synthesis ◽  
Dna Lesions ◽  
Replication Forks ◽  
Dna Replication And Repair ◽  
Radiation Induced ◽  
Break Induced Replication

Abstract Here, we survey the diverse functions of DNA polymerase ζ (pol ζ) in eukaryotes. In mammalian cells, REV3L (3130 residues) is the largest catalytic subunit of the DNA polymerases. The orthologous subunit in yeast is Rev3p. Pol ζ also includes REV7 subunits (encoded by Rev7 in yeast and MAD2L2 in mammalian cells) and two subunits shared with the replicative DNA polymerase, pol δ. Pol ζ is used in response to circumstances that stall DNA replication forks in both yeast and mammalian cells. The best-examined situation is translesion synthesis at sites of covalent DNA lesions such as UV radiation-induced photoproducts. We also highlight recent evidence that uncovers various roles of pol ζ that extend beyond translesion synthesis. For instance, pol ζ is also employed when the replisome operates sub-optimally or at difficult-to-replicate DNA sequences. Pol ζ also participates in repair by microhomology mediated break-induced replication. A rev3 deletion is tolerated in yeast but Rev3l disruption results in embryonic lethality in mice. Inactivation of mammalian Rev3l results in genomic instability and invokes cell death and senescence programs. Targeting of pol ζ function may be a useful strategy in cancer therapy, although chromosomal instability associated with pol ζ deficiency must be considered.

Abundance of cyclin B1 regulates γ-radiation–induced apoptosis

Blood ◽  
2000 ◽  
Vol 95 (8) ◽  
pp. 2645-2650 ◽  
Author(s):  
Lisa A. Porter ◽  
Gurmit Singh ◽  
Jonathan M. Lee
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Mammalian Cells ◽  
Hematopoietic Cells ◽  
Cyclin B1 ◽  
Regulatory Subunit ◽  
Potent Inducer ◽  
Γ Radiation ◽  
Radiation Induced ◽  
Induced Apoptosis

Abstract γ-Radiation is a potent inducer of apoptosis. There are multiple pathways regulating DNA damage-induced apoptosis, and we set out to identify novel mechanisms regulating γ-radiation–induced apoptosis in hematopoietic cells. In this report, we present data implicating the cyclin B1 protein as a regulator of apoptotic fate following DNA damage. Cyclin B1 is the regulatory subunit of the cdc2 serine/threonine kinase, and accumulation of cyclin B1 in late G2 phase of the cell cycle is a prerequisite for mitotic initiation in mammalian cells. We find that abundance of the cyclin B1 protein rapidly increases in several mouse and human hematopoietic cells (Ramos, DP16, HL60, thymocytes) undergoing γ-radiation–induced apoptosis. Cyclin B1 accumulation occurs in all phases of the cell cycle. Antisense inhibition of cyclin B1 accumulation decreases apoptosis, and ectopic cyclin B1 expression is sufficient to induce apoptosis. These observations are consistent with the idea that cyclin B1 is both necessary and sufficient for γ-radiation-induced apoptosis.

scholarly journals DNA binding properties of human DNA polymerase η: implications for fidelity and polymerase switching of translesion synthesis

2004 ◽  
Vol 9 (12) ◽  
pp. 1139-1150 ◽  
Author(s):  
Rika Kusumoto ◽  
Chikahide Masutani ◽  
Shizu Shimmyo ◽  
Shigenori Iwai ◽  
Fumio Hanaoka
Keyword(s):  
Dna Binding ◽  
Dna Polymerase ◽  
Translesion Synthesis ◽  
Binding Properties ◽  
Human Dna ◽  
Dna Binding Properties

scholarly journals Translesion Synthesis past Acrolein-derived DNA Adduct, γ-Hydroxypropanodeoxyguanosine, by Yeast and Human DNA Polymerase η

2002 ◽  
Vol 278 (2) ◽  
pp. 784-790 ◽  
Author(s):  
Irina G. Minko ◽  
M. Todd Washington ◽  
Manorama Kanuri ◽  
Louise Prakash ◽  
Satya Prakash ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Translesion Synthesis ◽  
Dna Adduct ◽  
Human Dna
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