The concerted roles of FANCM and Rad52 in the protection of common fragile sites.

Nature Communications
Hailong WangXiaohua Wu

Abstract

Common fragile sites (CFSs) are prone to chromosomal breakage and are hotspots for chromosomal rearrangements in cancer cells. We uncovered a novel function of Fanconi anemia (FA) protein FANCM in the protection of CFSs that is independent of the FA core complex and the FANCI-FANCD2 complex. FANCM, along with its binding partners FAAP24 and MHF1/2, is recruited to CFS-derived structure-prone AT-rich sequences, where it suppresses DNA double-strand break (DSB) formation and mitotic recombination in a manner dependent on FANCM translocase activity. Interestingly, we also identified an indispensable function of Rad52 in the repair of DSBs at CFS-derived AT-rich sequences, despite its nonessential function in general homologous recombination (HR) in mammalian cells. Suppression of Rad52 expression in combination with FANCM knockout drastically reduces cell and tumor growth, suggesting a synthetic lethality interaction between these two genes, which offers a potential targeted treatment strategy for FANCM-deficient tumors with Rad52 inhibition.

References

Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·T Tsuzuki MoritaT
Jan 16, 2003·Cell·Anne M CasperThomas W Glover
Jul 31, 2003·Cell·Kenkichi MasutomiWilliam C Hahn
Jul 16, 2004·Molecular and Cellular Biology·Martin F ArltThomas W Glover
Jan 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Koji NakanishiMaria Jasin
Apr 15, 2005·Nature·Vassilis G GorgoulisThanos D Halazonetis
Aug 24, 2005·Nature Structural & Molecular Biology·Georgina MosedaleKetan J Patel
Jun 30, 2006·DNA Repair·Martin F ArltThomas W Glover
Dec 1, 2006·Nature·Raffaella Di MiccoFabrizio d'Adda di Fagagna
Apr 6, 2007·ORL; Journal for Oto-rhino-laryngology and Its Related Specialties·Volkert B WreesmannSteven J Wang
Jun 27, 2007·Molecular and Cellular Biology·Erin OlsonXiaohua Wu
Jul 5, 2007·Annual Review of Genetics·Sandra G Durkin, Thomas W Glover
Dec 15, 2007·Biochimica Et Biophysica Acta·T Lukusa, J P Fryns
Jan 4, 2008·The Journal of Biological Chemistry·Longchuan ChenXiaohua Wu
Oct 10, 2008·Proceedings of the National Academy of Sciences of the United States of America·Kerstin GariAngelos Constantinou
May 26, 2009·Nature Cell Biology·Kok Lung ChanIan D Hickson
Jun 30, 2009·Human Molecular Genetics·Sietske T BakkerJohan P de Winter
Aug 27, 2009·Current Biology : CB·Uffe H MortensenRodney Rothstein
Jan 9, 2010·The EMBO Journal·Rebekka A SchwabWojciech Niedzwiedz
Jan 13, 2010·Molecular Cell·Andrew J Deans, Stephen C West
Aug 24, 2010·Nature·Ryan B JensenStephen C Kowalczykowski
Dec 15, 2010·Proceedings of the National Academy of Sciences of the United States of America·Zhihui FengSimon N Powell
Dec 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jie Liu, Wolf-Dietrich Heyer
Mar 23, 2011·Nature Structural & Molecular Biology·Koji NakanishiMaria Jasin
Nov 19, 2011·Trends in Genetics : TIG·Michelle DebatisseOlivier Brison
May 1, 2012·The Journal of Biological Chemistry·Hailong WangXiaohua Wu

❮ Previous
Next ❯

Citations

Dec 14, 2018·Genes, Chromosomes & Cancer·Michal Irony-Tur Sinai, Batsheva Kerem
Feb 5, 2019·Critical Reviews in Biochemistry and Molecular Biology·Jihane Basbous, Angelos Constantinou
Aug 15, 2019·Nucleic Acids Research·Michal Irony-Tur SinaiBatsheva Kerem
May 30, 2019·Nature Communications·Robert LuHilda A Pickett
Mar 6, 2019·International Journal of Molecular Sciences·Nagendra VermaClaudio Talora
Sep 26, 2019·Frontiers in Molecular Biosciences·Beatriz Domingues-SilvaClaus M Azzalin
Mar 14, 2020·Cell & Bioscience·Shibo Li, Xiaohua Wu
Mar 21, 2020·Cancers·Vanesa Gottifredi, Lisa Wiesmüller
Jul 26, 2019·Cancers·Manisha JalanSimon N Powell
Oct 30, 2020·Molecular Genetics & Genomic Medicine·Lisa A Cannon-AlbrightSean V Tavtigian
Jan 21, 2021·The EMBO Journal·Shibo LiXiaohua Wu
Nov 19, 2020·Trends in Cancer·Katherine E Baillie, Peter C Stirling
Dec 15, 2020·Current Opinion in Cell Biology·Aleksandra Lezaja, Matthias Altmeyer
Sep 10, 2021·Nucleic Acids Research·Abhishek Bharadwaj SharmaEric Van Dyck
Oct 15, 2019·Cell·Tatiana García-Muse, Andrés Aguilera

❮ Previous
Next ❯

Methods Mentioned

BETA
ChIP
PCR
xenograft
fluorescence-activated cell sorting
FACS
electrophoresis
immunoprecipitation

Software Mentioned

TTEST
Image J

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.