AlkB demethylases flip out in different ways

DNA Repair
Ottar SundheimHans E Krokan

Abstract

Aberrant methylations in DNA are repaired by base excision repair (BER) and direct repair by a methyltransferase or by an oxidative demethylase of the AlkB type. Yang et al. [Nature 452 (2008) 961-966] have now solved the crystal structure of AlkB and human AlkB homolog 2 (hABH2) in complex with DNA using an ingenious crosslinking strategy to stabilize the DNA-protein complex. AlkB proteins have similar catalytic domains, but different DNA recognition motifs. Whereas AlkB mainly makes contact with the damaged strand, hABH2 makes numerous contacts with both strands. hABH2 flips out the damaged base and fills the vacant space by a hydrophobic amino acid residue similar to DNA glycosylases, essentially without distorting the double helix structure. In contrast, AlkB squeezes together the bases flanking the flipped-out base to maintain the base stack. This unprecedented flipping mechanism and the differences between AlkB and hABH2 in contacting the DNA strands explain their preferences for single stranded- and double stranded DNA, respectively.

References

Apr 13, 2001·Bioinformatics·C Gille, C Frömmel
Dec 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tod DuncanBarbara Sedgwick
Feb 13, 2004·Bioinformatics·Michele ClampGeoffrey J Barton
Mar 26, 2004·Nature Reviews. Molecular Cell Biology·Barbara Sedgwick
Sep 24, 2004·DNA Repair·Finn DrabløsHans E Krokan
Apr 26, 2005·Nucleic Acids Research·Yang Zhang, Jeffrey Skolnick
Sep 22, 2005·The Journal of Biological Chemistry·Dong-Hyun LeeTimothy R O'Connor
Dec 19, 2006·Neuroscience·P Ø FalnesI Alseth
Jun 4, 2008·Cancer Research·Jeanette RingvollArne Klungland

❮ Previous
Next ❯

Citations

Jul 20, 2010·Interdisciplinary Sciences, Computational Life Sciences·G Andrés Cisneros
Dec 22, 2012·Neuro-oncology·Tor-Christian Aase JohannessenRolf Bjerkvig
Mar 4, 2014·Chemical Reviews·Guanqun ZhengChuan He
Mar 28, 2009·Environmental and Molecular Mutagenesis·Wen-Hsing Cheng
Mar 16, 2013·EMBO Reports·Asun Monfort, Anton Wutz
Jul 15, 2015·DNA Repair·Irfan KhanRobert M Brosh
Aug 21, 2010·Journal of Nucleic Acids·Gaëlle Lenglet, Marie-Hélène David-Cordonnier
Aug 22, 2015·International Journal of Endocrinology·Yeng F Her, L James Maher
Dec 3, 2014·Journal of Molecular Graphics & Modelling·Pavel SilvestrovG Andrés Cisneros
Apr 3, 2012·Experimental Parasitology·Jana M SimmonsRobert P Hausinger
May 9, 2014·FEMS Microbiology Letters·Damian Mielecki, Elżbieta Grzesiuk
Nov 7, 2016·Trends in Biochemical Sciences·Jennifer M SollNima Mosammaparast
Oct 10, 2014·Beilstein Journal of Organic Chemistry·Christine Beuck, Elmar Weinhold
Feb 14, 2020·Cell Research·Min ZhangHaitao Li
Mar 13, 2014·The Journal of Biological Chemistry·Chong FengZhongzhou Chen
Jun 3, 2018·Biomolecular NMR Assignments·Jeffrey A Purslow, Vincenzo Venditti
Jul 10, 2020·Cellular and Molecular Life Sciences : CMLS·Baofang XuYongchun Zuo
Jan 30, 2021·Frontiers in Cell and Developmental Biology·Mahmoud Bayoumi, Muhammad Munir
May 22, 2020·DNA Repair·Natalie Saini, Dmitry A Gordenin

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.