Constitutively active Artemis nuclease recognizes structures containing single-stranded DNA configurations

DNA Repair
Nicholas R Pannunzio, Michael R Lieber

Abstract

The Artemis nuclease recognizes and endonucleolytically cleaves at single-stranded to double-stranded DNA (ss/dsDNA) boundaries. It is also a key enzyme in the non-homologous end joining (NHEJ) DNA double-strand break repair pathway. Previously, a truncated form, Artemis-413, was developed that is constitutively active both in vitro and in vivo. Here, we use this constitutively active form of Artemis to detect DNA structures with ss/dsDNA boundaries that arise under topological stress. Topoisomerases prevent abnormal levels of torsional stress through modulation of positive and negative supercoiling. We show that overexpression of Artemis-413 in yeast cells carrying genetic mutations that ablate topoisomerase activity have an increased frequency of DNA double-strand breaks (DSBs). Based on the biochemical activity of Artemis, this suggests an increase in ss/dsDNA-containing structures upon increased torsional stress, with DSBs arising due to Artemis cutting at these ss/dsDNA structures. Camptothecin targets topoisomerase IB (Top1), and cells treated with camptothecin show increased DSBs. We find that expression of Artemis-413 in camptothecin-treated cells leads to a reduction in DSBs, the opposite of what we find with topoisome...Continue Reading

References

Mar 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·K StruhlR W Davis
Feb 24, 1989·Cell·B J Thomas, R Rothstein
Oct 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·L F Liu, J C Wang
Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·J Nitiss, J C Wang
Jul 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·C ThrashR Sternglanz
May 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·S DiNardoR Sternglanz
Mar 3, 1995·The Journal of Biological Chemistry·J J Harrington, M R Lieber
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·S W YangH A Nash
Nov 24, 1999·The Journal of Biological Chemistry·G PetukhovaP Sung
Oct 31, 2000·The Journal of Biological Chemistry·S Trigueros, J Roca
May 17, 2001·The Journal of Biological Chemistry·J L NitissJ L Waltman
Jun 4, 2002·Nature Reviews. Molecular Cell Biology·James C Wang
Oct 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·John R Vance, Thomas E Wilson
Apr 9, 2004·The EMBO Journal·Ulrich PannickeKlaus Schwarz
Jun 7, 2005·DNA Repair·Yunmei MaMichael R Lieber
Aug 12, 2005·The Journal of Biological Chemistry·Yunmei MaMichael R Lieber
Nov 16, 2005·Annual Review of Genetics·James M DaleyThomas E Wilson
Jul 22, 2006·DNA Repair·Carolyn A FelixNeil Osheroff
Jul 29, 2006·The EMBO Journal·Aaron A GoodarziSusan P Lees-Miller
Aug 18, 2006·The Journal of Biological Chemistry·Doris NiewolikKlaus Schwarz
Nov 17, 2007·DNA Repair·Ali HazratiPeter J McHugh
Apr 2, 2008·Chemical Research in Toxicology·Pierantonio MennaGiorgio Minotti
Aug 22, 2008·Nature·Pablo HuertasStephen P Jackson
Apr 21, 2009·Nature Reviews. Cancer·John L Nitiss
Apr 21, 2009·Nature Reviews. Cancer·John L Nitiss
Feb 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Karim BahmedJohn L Nitiss
Jul 26, 2011·Journal of Radiation Research·Takanori KatsubeMakoto Onoda
Aug 31, 2011·Molecular and Cellular Biology·Steven S FosterJohn H J Petrini
Nov 22, 2011·Nucleic Acids Research·Tracy Tiefenbach, Murray Junop
Feb 15, 2012·Nature Reviews. Genetics·Nayun Kim, Sue Jinks-Robertson
Dec 25, 2012·ACS Chemical Biology·Yves Pommier
Feb 19, 2013·Nature Structural & Molecular Biology·Fedor KouzineDavid Levens

❮ Previous
Next ❯

Citations


❮ 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.