Chemistry of Thermal Degradation of Abasic Sites in DNA. Mechanistic Investigation on Thermal DNA Strand Cleavage of Alkylated DNA

1994 ◽  
Vol 7 (5) ◽  
pp. 673-683 ◽  
Author(s):  
Hiroshi Sugiyama ◽  
Tsuyoshi Fujiwara ◽  
Atsushi Ura ◽  
Takahisa Tashiro ◽  
Koji Yamamoto ◽  
...  
1989 ◽  
Vol 111 (20) ◽  
pp. 8029-8030 ◽  
Author(s):  
Abhijit Mazumder ◽  
John A. Gerlt ◽  
Lois Rabow ◽  
Michael J. Absalon ◽  
JoAnne Stubbe ◽  
...  

2018 ◽  
Author(s):  
◽  
Zhiyu Yang

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Abasic sites (apurinic/apyrimidinic sites, Ap sites) are one of the most common forms of lesions found in genomic DNA. For the past decade, Gates group has endeavored to identify DNA interstrand crosslinks arising from Ap sites, that are sources of endogenous interstrand crosslinks which relate to aging, cancer and neurodegenerative diseases. This thesis describes my work in this area, starting from studying the DNA strand cleavage at abasic sites via [beta]-elimination reaction, that can generate a family of structurally diverse sugar remnants at the 3’ terminus of the nicked strand under physiological conditions. Using an in vitro system, I have characterized a series of DNA interstrand crosslinks arising from these single strand breaks, which structures are dependent on changing DNA sequence contexts and varied assay conditions that are all bio-relevant. These structures are novel and haven’t been reported to the best of our knowledge. In the meantime, this work has highlighted amine catalysis in Michael addition, and brought to attention the role of GSH in the formation of complex DNA lesions.


2001 ◽  
Vol 21 (5) ◽  
pp. 1656-1661 ◽  
Author(s):  
Ildiko Unk ◽  
Lajos Haracska ◽  
Satya Prakash ◽  
Louise Prakash

ABSTRACT In Saccharomyces cerevisiae, the AP endonucleases encoded by the APN1 and APN2 genes provide alternate pathways for the removal of abasic sites. Oxidative DNA-damaging agents, such as H2O2, produce DNA strand breaks which contain 3′-phosphate or 3′-phosphoglycolate termini. Such 3′ termini are inhibitory to synthesis by DNA polymerases. Here, we show that purified yeast Apn2 protein contains 3′-phosphodiesterase and 3′→5′ exonuclease activities, and mutation of the active-site residue Glu59 to Ala in Apn2 inactivates both these activities. Consistent with these biochemical observations, genetic studies indicate the involvement of APN2 in the repair of H2O2-induced DNA damage in a pathway alternate to APN1, and the Ala59 mutation inactivates this function of Apn2. From these results, we conclude that the ability of Apn2 to remove 3′-end groups from DNA is paramount for the repair of strand breaks arising from the reaction of DNA with reactive oxygen species.


2020 ◽  
Author(s):  
Debarshi Mallick ◽  
Bhaskor Jyoti Bora ◽  
Debarshi Baruah ◽  
Sabir Ahmed Barbhuiya ◽  
Rajdeep Banik ◽  
...  

2004 ◽  
pp. 039-046
Author(s):  
Walter A. Deutsch ◽  
Vijay Hegde
Keyword(s):  

1997 ◽  
Vol 17 (9) ◽  
pp. 5437-5452 ◽  
Author(s):  
J Legault ◽  
A Tremblay ◽  
D Ramotar ◽  
M E Mirault

DNA end-labeling procedures were used to analyze both the frequency and distribution of DNA strand breaks in mammalian cells exposed or not to different types of DNA-damaging agents. The 3' ends were labeled by T4 DNA polymerase-catalyzed nucleotide exchange carried out in the absence or presence of Escherichia coli endonuclease IV to cleave abasic sites and remove 3' blocking groups. Using this sensitive assay, we show that DNA isolated from human cells or mouse tissues contains variable basal levels of DNA strand interruptions which are associated with normal bioprocesses, including DNA replication and repair. On the other hand, distinct dose-dependent patterns of DNA damage were assessed quantitatively in cultured human cells exposed briefly to menadione, methylmethane sulfonate, topoisomerase II inhibitors, or gamma rays. In vivo induction of single-strand breaks and abasic sites by methylmethane sulfonate was also measured in several mouse tissues. The genomic distribution of these lesions was investigated by DNA cleavage with the single-strand-specific S1 nuclease. Strikingly similar cleavage patterns were obtained with all DNA-damaging agents tested, indicating that the majority of S1-hypersensitive sites detected were not randomly distributed over the genome but apparently were clustered in damage-sensitive regions. The parallel disappearance of 3' ends and loss of S1-hypersensitive sites during post-gamma-irradiation repair periods indicates that these sites were rapidly repaired single-strand breaks or gaps (2- to 3-min half-life). Comparison of S1 cleavage patterns obtained with gamma-irradiated DNA and gamma-irradiated cells shows that chromatin structure was the primary determinant of the distribution of the DNA damage detected.


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