Mechanism of Holliday junction resolution by the human GEN1 protein.

Genes & Development
Ulrich RassStephen C West

Abstract

Holliday junction (HJ) resolution is essential for chromosome segregation at meiosis and the repair of stalled/collapsed replication forks in mitotic cells. All organisms possess nucleases that promote HJ resolution by the introduction of symmetrically related nicks in two strands at, or close to, the junction point. GEN1, a member of the Rad2/XPG nuclease family, was isolated recently from human cells and shown to promote HJ resolution in vitro and in vivo. Here, we provide the first biochemical/structural characterization of GEN1, showing that, like the Escherichia coli HJ resolvase RuvC, it binds specifically to HJs and resolves them by a dual incision mechanism in which nicks are introduced in the pair of continuous (noncrossing) strands within the lifetime of the GEN1-HJ complex. In contrast to RuvC, but like other Rad2/XPG family members such as FEN1, GEN1 is a monomeric 5'-flap endonuclease. However, the unique feature of GEN1 that distinguishes it from other Rad2/XPG nucleases is its ability to dimerize on HJs. This functional adaptation provides the two symmetrically aligned active sites required for HJ resolution.

References

Jan 1, 1978·Annual Review of Biophysics and Bioengineering·J D Griffith, G Christiansen
Oct 7, 1988·Cell·D R DuckettD M Lilley
Mar 10, 1995·Journal of Molecular Biology·J D GriffithD Reinberg
Mar 14, 1997·The Journal of Biological Chemistry·S LeeJ Griffith
Mar 1, 1997·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·M R Lieber
Oct 23, 1997·Genes & Development·G S Roeder
Jan 1, 1997·Annual Review of Genetics·S C West
Aug 1, 1998·Nucleic Acids Research·D M WilsonJ E Lamerdin
Jun 5, 1999·Microbiology and Molecular Biology Reviews : MMBR·F Pâques, J E Haber
Mar 15, 2000·Nature·M M CoxK J Marians
Jul 13, 2000·Proceedings of the National Academy of Sciences of the United States of America·A D GarciaB Moss
Aug 15, 2000·The Journal of Biological Chemistry·M KvaratskheliaM F White
Aug 16, 2000·Proceedings of the National Academy of Sciences of the United States of America·D M Lilley, M F White
Dec 29, 2000·Quarterly Reviews of Biophysics·D M Lilley
Jun 5, 2001·Nature Reviews. Molecular Cell Biology·D M Lilley, M F White
Jun 27, 2002·The Journal of Biological Chemistry·Claudette L DoeMatthew C Whitby
Dec 24, 2002·Nature Structural Biology·Sean A McKinneyTaekjip Ha
Mar 20, 2003·The Journal of Biological Chemistry·Marcel HohlOrlando D Schärer
May 2, 2003·The Journal of Biological Chemistry·Alberto CicciaStephen C West
Oct 24, 2003·Nature·Jeffrey A UbersaxDavid O Morgan
May 4, 2005·Cancer Research·Mahmoud El-ShemerlyStefano Ferrari
Jun 15, 2005·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Binghui ShenSteve Alas
Oct 6, 2005·The Journal of Biological Chemistry·Deepa Subramanian, Jack D Griffith
Jun 24, 2006·Methods in Enzymology·Ulrich Rass, Stephen C West
Jul 22, 2006·Annual Review of Genetics·Leonard Wu, Ian D Hickson
Jun 8, 2007·Nucleic Acids Research·Chung-Tsai SuChen-Ming Hsu
Sep 18, 2007·Nature·Jonathan M HaddenSimon E V Phillips
Sep 18, 2007·Nature·Christian BiertümpfelDietrich Suck

❮ Previous
Next ❯

Citations

Jan 1, 1989·Pharmacology & Therapeutics·S C Mitchell, R H Waring
Aug 26, 1999·International Journal of Pharmaceutics·W Wang
Jan 1, 1995·Folding & Design·R J Ellis
Apr 16, 2013·Nature Structural & Molecular Biology·Pierre-Marie DehéPierre-Henri L Gaillard
Mar 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Hocine W MankouriIan D Hickson
May 31, 2012·Molecular and Cellular Biology·Erin K SchwartzWolf-Dietrich Heyer
Dec 29, 2013·Nucleic Acids Research·Alessandra Pepe, Stephen C West
May 12, 2011·Current Gerontology and Geriatrics Research·Michel LebelVilhelm A Bohr
Sep 12, 2014·Nature Communications·Ying Wai Chan, Stephen C West
Aug 15, 2014·Nucleic Acids Research·Michał MiętusMarcin Nowotny
Jun 15, 2014·FEBS Letters·Zdenka Bartosova, Lumir Krejci
Oct 16, 2014·Journal of Molecular Biology·Alasdair D J FreemanDavid M J Lilley
Nov 29, 2011·Trends in Biochemical Sciences·Jane A GrasbyJohn A Tainer
Dec 22, 2015·Cell Reports·Yijin LiuDavid M J Lilley
Sep 25, 2015·Nucleic Acids Research·Feng ZhangXiaochun Yu
Nov 19, 2015·Nucleic Acids Research·Ying Wai Chan, Stephen West
Feb 24, 2016·Pharmacology & Therapeutics·Pounami SamadderLumir Krejci
Jul 2, 2014·Journal of Biochemical and Molecular Toxicology·Lihua SunXingyi Zhang
Dec 5, 2012·Journal of Molecular Biology·Alasdair D J FreemanDavid M J Lilley
Aug 19, 2015·Frontiers in Genetics·Miguel G Blanco, Joao Matos
Dec 24, 2013·Trends in Cell Biology·Sheroy Minocherhomji, Ian D Hickson
Aug 19, 2014·Trends in Biochemical Sciences·Shriparna Sarbajna, Stephen C West
Apr 29, 2014·DNA Repair·Joao Matos, Stephen C West
May 23, 2014·Frontiers in Plant Science·Ding TangZhukuan Cheng

❮ 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.