The rate of formation and stability of abasic site interstrand crosslinks in the DNA duplex

0556771 - ÚOCHB 2023 RIV NL eng J - Journal Article
Hušková, Andrea - Landová, Barbora - Bouřa, Evžen - Šilhán, Jan
The rate of formation and stability of abasic site interstrand crosslinks in the DNA duplex.
Dna Repair. Roč. 113, May (2022), č. článku 103300. ISSN 1568-7864. E-ISSN 1568-7856
R&D Projects: GA ČR(CZ) GJ17-21649Y
Institutional support: RVO:61388963
Keywords : DNA damage * interstrand crosslink * abasic site * non-enzyme kinetics * DNA repair
OECD category: Biochemistry and molecular biology
Impact factor: 3.8, year: 2022
Method of publishing: Limited access
https://doi.org/10.1016/j.dnarep.2022.103300

DNA interstrand crosslinks (ICLs) strands pose an impenetrable barrier for DNA replication. Different ICLs are known to recruit distinct DNA repair pathways. NEIL3 glycosylase has been known to remove an abasic (Ap) site derived DNA crosslink (Ap-ICL). An Ap-ICL forms spontaneously from the Ap site with an adjacent adenine in the opposite strand. Lack of genetic models and a poor understanding of the fate of these lesions leads to many questions about the occurrence and the toxicity of Ap-ICL in cells. Here, we investigate the circumstances of Ap-ICL formation. With an array of different oligos, we have investigated the rates of formation, the yields, and the stability of Ap-ICL. Our findings point out how different bases in the vicinity of the Ap site change crosslink formation in vitro. We reveal that AT-rich rather than GC-rich regions in the surrounding Ap site lead to higher rates of Ap-ICL formation. Overall, our data reveal that Ap-ICL can be formed in virtually any DNA sequence context surrounding a hot spot of a 5′-Ap-dT pair, albeit with significantly different rates and yields. Based on Ap-ICL formation in vitro, we attempt to predict the number of Ap-ICLs in the cell.
Permanent Link: http://hdl.handle.net/11104/0330959