Ssu72 phosphatase is a conserved telomere replication terminator

The EMBO Journal
Jose Miguel EscandellMiguel Godinho Ferreira

Abstract

Telomeres, the protective ends of eukaryotic chromosomes, are replicated through concerted actions of conventional DNA polymerases and elongated by telomerase, but the regulation of this process is not fully understood. Telomere replication requires (Ctc1/Cdc13)-Stn1-Ten1, a telomeric ssDNA-binding complex homologous to RPA Here, we show that the evolutionarily conserved phosphatase Ssu72 is responsible for terminating the cycle of telomere replication in fission yeast. Ssu72 controls the recruitment of Stn1 to telomeres by regulating Stn1 phosphorylation at Ser74, a residue located within its conserved OB-fold domain. Consequently, ssu72∆ mutants are defective in telomere replication and exhibit long 3'-ssDNA overhangs, indicative of defective lagging-strand DNA synthesis. We also show that hSSU72 regulates telomerase activation in human cells by controlling recruitment of hSTN1 to telomeres. These results reveal a previously unknown yet conserved role for the phosphatase SSU72, whereby this enzyme controls telomere homeostasis by activating lagging-strand DNA synthesis, thus terminating the cycle of telomere replication.

References

Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·J J Lin, V A Zakian
Mar 7, 2001·Genes & Development·A ChandraV Lundblad
Apr 17, 2003·Molecular and Cellular Biology·Maria DahlénTeresa S-F Wang
Oct 16, 2003·Molecular and Cellular Biology·Eishi NoguchiPaul Russell
May 6, 2004·Molecular Cell·Shankarling KrishnamurthyMichael Hampsey
Jan 22, 2005·Nucleic Acids Research·Benoit St-PierreEldad Zacksenhaus
Apr 7, 2006·Nature·Kyle M MillerJulia Promisel Cooper
Aug 24, 2007·Proceedings of the National Academy of Sciences of the United States of America·Victoria MartínPaul Russell
Aug 6, 2008·Annual Review of Genetics·Wilhelm Palm, Titia de Lange
Mar 17, 2009·Molecular Cell·Ofer RogJulia Promisel Cooper
Nov 10, 2009·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Bettina A Moser, Toru M Nakamura
Sep 11, 2010·Nature·Tiago CarneiroMiguel Godinho Ferreira
Sep 14, 2010·Molecular Cell·Marie-Josèphe Giraud-PanisEric Gilson
Nov 16, 2010·Nature Structural & Molecular Biology·Sophie BadieMadalena Tarsounas
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Jul 12, 2011·Nature Structural & Molecular Biology·Lisa E HangXiaolan Zhao
Nov 22, 2011·Nature Structural & Molecular Biology·Bettina A MoserToru M Nakamura
May 5, 2012·Science·Agnel Sfeir, Titia de Lange
Jul 6, 2012·Nature·Liuh-Yow ChenJoachim Lingner
Jan 12, 2013·Science·Michal ZimmermannTitia de Lange
Mar 20, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yi ZhangZhou Songyang
Apr 2, 2014·Cell Reports·Stefano MattarocciDavid Shore
Apr 9, 2014·Proceedings of the National Academy of Sciences of the United States of America·Keisuke MiyagawaKatsunori Tanaka
Jun 20, 2014·PLoS Genetics·Vincent VanoosthuysePascal Bernard
Oct 13, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Se-Hyuk KimChang-Woo Lee
Jun 7, 2016·The FEBS Journal·Andrés Alonso, Rafael Pulido
Jul 13, 2016·Genes & Development·Carol W Greider

❮ Previous
Next ❯

Citations

Mar 30, 2021·DNA Repair·Xinxing LyuWeihang Chai
May 1, 2021·International Journal of Molecular Sciences·Soeun HwangChang-Woo Lee

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
ChIP
PCR

Software Mentioned

Protein Pilot
ProteinPilot
softWoRx

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.