The rate of base excision repair of uracil is controlled by the initiating glycosylase

DNA Repair
Torkild VisnesH E Krokan

Abstract

Uracil in DNA is repaired by base excision repair (BER) initiated by a DNA glycosylase, followed by strand incision, trimming of ends, gap filling and ligation. Uracil in DNA comes in two distinct forms; U:A pairs, typically resulting from replication errors, and mutagenic U:G mismatches, arising from cytosine deamination. To identify proteins critical to the rate of repair of these lesions, we quantified overall repair of U:A pairs, U:G mismatches and repair intermediates (abasic sites and nicked abasic sites) in vitro. For this purpose we used circular DNA substrates and nuclear extracts of eight human cell lines with wide variation in the content of BER proteins. We identified the initiating uracil-DNA glycosylase UNG2 as the major overall rate-limiting factor. UNG2 is apparently the sole glycosylase initiating BER of U:A pairs and generally initiated repair of almost 90% of the U:G mismatches. Surprisingly, TDG contributed at least as much as single-strand selective monofunctional uracil-DNA glycosylase 1 (SMUG1) to BER of U:G mismatches. Furthermore, in a cell line that expressed unusually high amounts of TDG, this glycosylase contributed to initiation of as much as approximately 30% of U:G repair. Repair of U:G mismatches...Continue Reading

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Citations

Jan 9, 2010·The Journal of Biological Chemistry·Dolores Córdoba-CañeroTeresa Roldán-Arjona
Jul 19, 2012·Biochemistry. Biokhimii︠a︡·A G DerevyankoD O Zharkov
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Aug 18, 2009·The Plant Journal : for Cell and Molecular Biology·Dolores Córdoba-CañeroRafael R Ariza
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Aug 23, 2019·Current HIV Research·Hesna KaraSerge Bouaziz
Oct 3, 2020·Scientific Reports·Berna SomuncuMeltem Muftuoglu
Jun 22, 2014·The Journal of Biological Chemistry·Bork LühnsdorfAndriy Khobta
Jul 23, 2013·Molecular Cancer Therapeutics·Lachelle D WeeksStanton L Gerson
Dec 19, 2009·The Journal of Organic Chemistry·Yu Lin JiangAvani Javer
Aug 28, 2021·International Journal of Molecular Sciences·Marina Jordano-RayaDolores Córdoba-Cañero

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