TY - JOUR

T1 - The hidden elephant: Modified abasic sites and their consequences

AU - Yudkina, Anna V.

AU - Zharkov, Dmitry O.

N1 - This research was supported by Russian Science Foundation (grant 21-64-00017). Partial salary support from the Russian Ministry of Science and Higher Education is acknowledged (125012300657-2).

PY - 2025/4

Y1 - 2025/4

N2 - Abasic, or apurinic/apyrimidinic sites (AP sites) are among the most abundant DNA lesions, appearing in DNA both through spontaneous base loss and as intermediates of base excision DNA repair. Natural aldehydic AP sites have been known for decades and their interaction with the cellular replication, transcription and repair machinery has been investigated in detail. Oxidized AP sites, produced by free radical attack on intact nucleotides, received much attention recently due to their ability to trap DNA repair enzymes and chromatin structural proteins such as histones. In the past few years, it became clear that the reactive nature of aldehydic and oxidized AP sites produces a variety of modifications, including AP site–protein and AP site–peptide cross-links, adducts with small molecules of metabolic or xenobiotic origin, and AP site-mediated interstrand DNA cross-links. The diverse chemical nature of these common-origin lesions is reflected in the wide range of their biological consequences. In this review, we summarize the data on the mechanisms of modified AP sites generation, their abundance, the ability to block DNA polymerases or cause nucleotide misincorporation, and the pathways of their repair.

AB - Abasic, or apurinic/apyrimidinic sites (AP sites) are among the most abundant DNA lesions, appearing in DNA both through spontaneous base loss and as intermediates of base excision DNA repair. Natural aldehydic AP sites have been known for decades and their interaction with the cellular replication, transcription and repair machinery has been investigated in detail. Oxidized AP sites, produced by free radical attack on intact nucleotides, received much attention recently due to their ability to trap DNA repair enzymes and chromatin structural proteins such as histones. In the past few years, it became clear that the reactive nature of aldehydic and oxidized AP sites produces a variety of modifications, including AP site–protein and AP site–peptide cross-links, adducts with small molecules of metabolic or xenobiotic origin, and AP site-mediated interstrand DNA cross-links. The diverse chemical nature of these common-origin lesions is reflected in the wide range of their biological consequences. In this review, we summarize the data on the mechanisms of modified AP sites generation, their abundance, the ability to block DNA polymerases or cause nucleotide misincorporation, and the pathways of their repair.

KW - AP sites

KW - DNA adducts

KW - DNA–peptide cross-links

KW - DNA–protein cross-links

KW - Interstrand cross-links

UR - https://www.mendeley.com/catalogue/aa759d94-adf2-3eb7-aebc-223d699171b0/

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85219681090&origin=inward&txGid=1ee73808875581b96984b35378174c0c

U2 - 10.1016/j.dnarep.2025.103823

DO - 10.1016/j.dnarep.2025.103823

M3 - Article

C2 - 40056494

VL - 148

JO - DNA Repair

JF - DNA Repair

SN - 1568-7864

M1 - 03823

ER -