A Role for N6-Methyladenine in DNA Damage Repair

Xing Zhang; Robert M. Blumenthal; Xiaodong Cheng

doi:10.1016/j.tibs.2020.09.007

A Role for N6-Methyladenine in DNA Damage Repair

Xing Zhang, Robert M. Blumenthal, Xiaodong Cheng

Epigenetics & Molecular Carcinogenesis

Research output: Contribution to journal › Review article › peer-review

13 Scopus citations

Abstract

The leading cause of mutation due to oxidative damage is 8-oxo-2′-deoxyguanosine (8-oxoG) mispairing with adenine (Ade), which can occur in two ways. First, guanine of a G:C DNA base pair can be oxidized. If not repaired in time, DNA polymerases can mispair Ade with 8-oxoG in the template. This 8-oxoG:A can be repaired by enzymes that remove Ade opposite to template 8-oxoG, or 8-oxoG opposite to Cyt. Second, free 8-oxo-dGTP can be misincorporated by DNA polymerases into DNA opposite template Ade. However, there is no known repair activity that removes 8-oxoG opposite to template Ade. We suggest that a major role of N6-methyladenine in mammalian DNA is minimizing incorporation of 8-oxoG opposite to Ade by DNA polymerases following adduct formation.

Original language	English (US)
Pages (from-to)	175-183
Number of pages	9
Journal	Trends in Biochemical Sciences
Volume	46
Issue number	3
DOIs	https://doi.org/10.1016/j.tibs.2020.09.007
State	Published - Mar 2021

Keywords

8-oxoguanine
DNA adenine methylation
MettL3-MettL14
YTHDC1
single-stranded DNA

ASJC Scopus subject areas

Biochemistry
Molecular Biology

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10.1016/j.tibs.2020.09.007

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title = "A Role for N6-Methyladenine in DNA Damage Repair",

abstract = "The leading cause of mutation due to oxidative damage is 8-oxo-2′-deoxyguanosine (8-oxoG) mispairing with adenine (Ade), which can occur in two ways. First, guanine of a G:C DNA base pair can be oxidized. If not repaired in time, DNA polymerases can mispair Ade with 8-oxoG in the template. This 8-oxoG:A can be repaired by enzymes that remove Ade opposite to template 8-oxoG, or 8-oxoG opposite to Cyt. Second, free 8-oxo-dGTP can be misincorporated by DNA polymerases into DNA opposite template Ade. However, there is no known repair activity that removes 8-oxoG opposite to template Ade. We suggest that a major role of N6-methyladenine in mammalian DNA is minimizing incorporation of 8-oxoG opposite to Ade by DNA polymerases following adduct formation.",

keywords = "8-oxoguanine, DNA adenine methylation, MettL3-MettL14, YTHDC1, single-stranded DNA",

author = "Xing Zhang and Blumenthal, {Robert M.} and Xiaodong Cheng",

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year = "2021",

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doi = "10.1016/j.tibs.2020.09.007",

language = "English (US)",

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T1 - A Role for N6-Methyladenine in DNA Damage Repair

AU - Zhang, Xing

AU - Blumenthal, Robert M.

AU - Cheng, Xiaodong

PY - 2021/3

Y1 - 2021/3

N2 - The leading cause of mutation due to oxidative damage is 8-oxo-2′-deoxyguanosine (8-oxoG) mispairing with adenine (Ade), which can occur in two ways. First, guanine of a G:C DNA base pair can be oxidized. If not repaired in time, DNA polymerases can mispair Ade with 8-oxoG in the template. This 8-oxoG:A can be repaired by enzymes that remove Ade opposite to template 8-oxoG, or 8-oxoG opposite to Cyt. Second, free 8-oxo-dGTP can be misincorporated by DNA polymerases into DNA opposite template Ade. However, there is no known repair activity that removes 8-oxoG opposite to template Ade. We suggest that a major role of N6-methyladenine in mammalian DNA is minimizing incorporation of 8-oxoG opposite to Ade by DNA polymerases following adduct formation.

AB - The leading cause of mutation due to oxidative damage is 8-oxo-2′-deoxyguanosine (8-oxoG) mispairing with adenine (Ade), which can occur in two ways. First, guanine of a G:C DNA base pair can be oxidized. If not repaired in time, DNA polymerases can mispair Ade with 8-oxoG in the template. This 8-oxoG:A can be repaired by enzymes that remove Ade opposite to template 8-oxoG, or 8-oxoG opposite to Cyt. Second, free 8-oxo-dGTP can be misincorporated by DNA polymerases into DNA opposite template Ade. However, there is no known repair activity that removes 8-oxoG opposite to template Ade. We suggest that a major role of N6-methyladenine in mammalian DNA is minimizing incorporation of 8-oxoG opposite to Ade by DNA polymerases following adduct formation.

KW - 8-oxoguanine

KW - DNA adenine methylation

KW - MettL3-MettL14

KW - YTHDC1

KW - single-stranded DNA

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JO - Trends in Biochemical Sciences

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A Role for N6-Methyladenine in DNA Damage Repair

Abstract

Keywords

ASJC Scopus subject areas

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