scholarly journals Cross-Link Structure Affects Replication-Independent DNA Interstrand Cross-Link Repair in Mammalian Cells

Biochemistry ◽  
2010 ◽  
Vol 49 (18) ◽  
pp. 3977-3988 ◽  
Author(s):  
Erica M. Hlavin ◽  
Michael B. Smeaton ◽  
Anne M. Noronha ◽  
Christopher J. Wilds ◽  
Paul S. Miller
Keyword(s):  
Mammalian Cells ◽  
Cross Link ◽  
Link Structure

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.

Vulcanization of Butadiene Rubber by Means of Cyclic Disulfides. 1. A 2D NMR Study on the Cross-Link Structure of a BR Model Compound Vulcanizate

1999 ◽  
Vol 32 (22) ◽  
pp. 7504-7508 ◽  
Author(s):  
Roger M. Seyger ◽  
Ron Hulst ◽  
John P. M. van Duynhoven ◽  
Robin Winters ◽  
Leen van der Does ◽  
...  
Keyword(s):  
Model Compound ◽  
2D Nmr ◽  
Butadiene Rubber ◽  
Cross Link ◽  
Link Structure ◽  
Nmr Study ◽  
The Cross

scholarly journals The Structure-Specific Endonuclease Ercc1-Xpf Is Required To Resolve DNA Interstrand Cross-Link-Induced Double-Strand Breaks

2004 ◽  
Vol 24 (13) ◽  
pp. 5776-5787 ◽  
Author(s):  
Laura J. Niedernhofer ◽  
Hanny Odijk ◽  
Magda Budzowska ◽  
Ellen van Drunen ◽  
Alex Maas ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Strand Break ◽  
Sister Chromatid Exchanges ◽  
Wild Type ◽  
Cross Link ◽  
Interstrand Cross Links ◽  
Normal Metabolism ◽  
Cross Links

ABSTRACT Interstrand cross-links (ICLs) are an extremely toxic class of DNA damage incurred during normal metabolism or cancer chemotherapy. ICLs covalently tether both strands of duplex DNA, preventing the strand unwinding that is essential for polymerase access. The mechanism of ICL repair in mammalian cells is poorly understood. However, genetic data implicate the Ercc1-Xpf endonuclease and proteins required for homologous recombination-mediated double-strand break (DSB) repair. To examine the role of Ercc1-Xpf in ICL repair, we monitored the phosphorylation of histone variant H2AX (γ-H2AX). The phosphoprotein accumulates at DSBs, forming foci that can be detected by immunostaining. Treatment of wild-type cells with mitomycin C (MMC) induced γ-H2AX foci and increased the amount of DSBs detected by pulsed-field gel electrophoresis. Surprisingly, γ-H2AX foci were also induced in Ercc1 −/− cells by MMC treatment. Thus, DSBs occur after cross-link damage via an Ercc1-independent mechanism. Instead, ICL-induced DSB formation required cell cycle progression into S phase, suggesting that DSBs are an intermediate of ICL repair that form during DNA replication. In Ercc1 −/− cells, MMC-induced γ-H2AX foci persisted at least 48 h longer than in wild-type cells, demonstrating that Ercc1 is required for the resolution of cross-link-induced DSBs. MMC triggered sister chromatid exchanges in wild-type cells but chromatid fusions in Ercc1 −/− and Xpf mutant cells, indicating that in their absence, repair of DSBs is prevented. Collectively, these data support a role for Ercc1-Xpf in processing ICL-induced DSBs so that these cytotoxic intermediates can be repaired by homologous recombination.

scholarly journals Initiation of DNA interstrand cross-link repair in humans: the nucleotide excision repair system makes dual incisions 5' to the cross-linked base and removes a 22- to 28-nucleotide-long damage-free strand.

1997 ◽  
Vol 17 (12) ◽  
pp. 6822-6830 ◽  
Author(s):  
T Bessho ◽  
D Mu ◽  
A Sancar
Keyword(s):  
Dna Repair ◽  
Mammalian Cells ◽  
Excision Repair ◽  
Repair System ◽  
Cross Link ◽  
Unique Challenge ◽  
Cell Extracts ◽  
Interstrand Cross Links ◽  
Cross Links ◽  
The Cross

Most DNA repair mechanisms rely on the redundant information inherent to the duplex to remove damaged nucleotides and replace them with normal ones, using the complementary strand as a template. Interstrand cross-links pose a unique challenge to the DNA repair machinery because both strands are damaged. To study the repair of interstrand cross-links by mammalian cells, we tested the activities of cell extracts of wild-type or excision repair-defective rodent cell lines and of purified human excision nuclease on a duplex with a site-specific cross-link. We found that in contrast to monoadducts, which are removed by dual incisions bracketing the lesion, the cross-link causes dual incisions, both 5' to the cross-link in one of the two strands. The net result is the generation of a 22- to 28-nucleotide-long gap immediately 5' to the cross-link. This gap may act as a recombinogenic signal to initiate cross-link removal.

scholarly journals Influence of Cross-Link Structure on Impact Strength of ABS.

1997 ◽  
Vol 54 (3) ◽  
pp. 148-155
Author(s):  
Kiyoshi IKAWA ◽  
Hajime SAKANO ◽  
Seiji TAMAI ◽  
Kazunori TAKAHASHI ◽  
Hiroshi KOJIMA
Keyword(s):  
Impact Strength ◽  
Cross Link ◽  
Link Structure

Polymerization Mechanism and Cross-Link Structure of Nadic End-Capped Polymers: A Quantum Mechanical and Microkinetic Investigation

2017 ◽  
Vol 50 (16) ◽  
pp. 6081-6087 ◽  
Author(s):  
Sooraj Kunnikuruvan ◽  
Priya V. Parandekar ◽  
Om Prakash ◽  
Thomas K. Tsotsis ◽  
Nisanth N. Nair
Keyword(s):  
Quantum Mechanical ◽  
Cross Link ◽  
Polymerization Mechanism ◽  
Link Structure
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