DNA with abasic sites has been prepared by deamination of cytosine followed by treatment of the product with uracil N-glycosylase. Termination in vitro on such templates does not occur until treatment with uracil N-glycosylase. DNA terminated one base before abasic sites created from C's has been used as a template in "second stage" reactions. With enzymes devoid or deficient in 3' greater than 5' exonuclease activity purines, particularly adenine, are preferentially added opposite the putative abasic site. 2-Aminopurine behaves more like adenine than like guanine in these experiments. Polymerase beta preferentially incorporates A opposite abasic sites produced from T, and G opposite abasic sites produced from C. We have eliminated an obvious artefact (e.g. strand switching) which might account for this observation.
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http://dx.doi.org/10.1093/nar/13.12.4285 | DOI Listing |
Int J Mol Sci
January 2025
Siberian Branch of the Russian Academy of Sciences Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentieva Ave., 630090 Novosibirsk, Russia.
The apurinic/apyrimidinic site (AP site) is a highly mutagenic and cytotoxic DNA lesion. Normally, AP sites are removed from DNA by base excision repair (BER). Methoxyamine (MOX), a BER inhibitor currently under clinical trials as a tumor sensitizer, forms adducts with AP sites (AP-MOX) resistant to the key BER enzyme, AP endonuclease.
View Article and Find Full Text PDFAbasic sites are one of the most frequent forms of DNA damage that interfere with DNA replication. However, abasic sites exhibit complex effects because they can be processed into other types of DNA damage. Thus, it remains poorly understood how abasic sites affect replisome progression, which replication-coupled repair pathways they elicit, and whether this is affected by the template strand that is damaged.
View Article and Find Full Text PDFBMB Rep
January 2025
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea.
Base excision repair (BER) is an essential cellular mechanism that repairs small, non-helix-distorting base lesions in DNA, resulting from oxidative damage, alkylation, deamination, or hydrolysis. This review highlights recent advances in understanding the molecular mechanisms of BER enzymes through single-molecule studies. We discuss the roles of DNA glycosylases in lesion recognition and excision, with a focus on facilitated diffusion mechanisms such as sliding and hopping that enable efficient genome scanning.
View Article and Find Full Text PDFBiochemistry
January 2025
Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
bioRxiv
November 2024
Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, CA, USA.
ATR is the master safeguard of genomic integrity during DNA replication. Acute inhibition of ATR with ATR inhibitor (ATRi) triggers a surge in origin firing, leading to increased levels of single-stranded DNA (ssDNA) that rapidly deplete all available RPA. This leaves ssDNA unprotected and susceptible to breakage, a phenomenon known as replication catastrophe.
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