Fanconi anemia group J mutation abolishes its DNA repair function by uncoupling DNA translocation from helicase activity or disruption of protein-DNA complexes.

Blood
Y WuRobert M Brosh

Abstract

Fanconi anemia (FA) is a genetic disease characterized by congenital abnormalities, bone marrow failure, and susceptibility to leukemia and other cancers. FANCJ, one of 13 genes linked to FA, encodes a DNA helicase proposed to operate in homologous recombination repair and replicational stress response. The pathogenic FANCJ-A349P amino acid substitution resides immediately adjacent to a highly conserved cysteine of the iron-sulfur domain. Given the genetic linkage of the FANCJ-A349P allele to FA, we investigated the effect of this particular mutation on the biochemical and cellular functions of the FANCJ protein. Purified recombinant FANCJ-A349P protein had reduced iron and was defective in coupling adenosine triphosphate (ATP) hydrolysis and translocase activity to unwinding forked duplex or G-quadruplex DNA substrates or disrupting protein-DNA complexes. The FANCJ-A349P allele failed to rescue cisplatin or telomestatin sensitivity of a FA-J null cell line as detected by cell survival or γ-H2AX foci formation. Furthermore, expression of FANCJ-A349P in a wild-type background exerted a dominant-negative effect, indicating that the mutant protein interferes with normal DNA metabolism. The ability of FANCJ to use the energy from A...Continue Reading

References

May 16, 2003·Nature·Lumir KrejciPatrick Sung
Feb 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sharon CantorDavid M Livingston
Nov 25, 2004·Journal of Molecular Biology·Christopher J FischerTimothy M Lohman
May 10, 2005·The Journal of Biological Chemistry·Rigu GuptaRobert M Brosh
Aug 24, 2005·Nature Genetics·Marieke LevitusHans Joenje
Aug 24, 2005·Nature Genetics·Orna LevranArleen D Auerbach
Nov 11, 2005·Breast Cancer Research : BCR·Aaron G LewisUNKNOWN Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer
Jan 25, 2006·BMC Cancer·Pia VahteristoHeli Nevanlinna
Sep 16, 2006·Molecular Cell·Jana RudolfMalcolm F White
May 17, 2007·BMC Cancer·Bernd FrankBarbara Burwinkel
Jul 31, 2007·Nature Structural & Molecular Biology·Dmitry V BugreevAlexander V Mazin
Aug 1, 2007·Molecular and Cellular Biology·Easwari Kumaraswamy, Ramin Shiekhattar
Oct 3, 2007·Cancer Research·Marianne BerwickArleen D Auerbach
Nov 16, 2007·Genes & Development·Dmitry V BugreevAlexander V Mazin
May 31, 2008·Cell·Huanting LiuMalcolm F White
Jun 27, 2008·PLoS Biology·Stefanie C WolskiCaroline Kisker
Jul 17, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Arcangela De NicoloMaria Adelaide Caligo
Nov 4, 2008·The Journal of Biological Chemistry·Timothy B C LondonKevin Hiom
Dec 17, 2008·The Journal of Biological Chemistry·Binbin RenHuangen Ding
Jan 20, 2009·The Journal of Biological Chemistry·Joshua A SommersRobert M Brosh
Apr 22, 2009·Mutation Research·Abdullah Mahmood AliAmom Ruhikanta Meetei
Jul 23, 2009·Mutation Research·Arleen D Auerbach
Aug 19, 2009·Annual Review of Genetics·George-Lucian Moldovan, Alan D D'Andrea

❮ Previous
Next ❯

Citations

Jul 12, 2013·Nature Reviews. Cancer·Robert M Brosh
Jan 31, 2012·Nucleic Acids Research·Yuliang Wu, Robert M Brosh
May 17, 2011·Biochemistry. Biokhimii︠a︡·J S Deakyne, A V Mazin
Feb 25, 2011·Future Oncology·Sharon B Cantor, Shawna Guillemette
Oct 29, 2013·Nucleic Acids Research·Alexander HendersonPeter M Lansdorp
Feb 4, 2014·Cellular and Molecular Life Sciences : CMLS·Sanjay Kumar BhartiRobert M Brosh
Jan 2, 2013·Mutation Research·Avvaru N Suhasini, Robert M Brosh
Dec 16, 2011·Current Opinion in Structural Biology·Malcolm F White, Mark S Dillingham
Oct 26, 2011·Trends in Genetics : TIG·Avvaru N Suhasini, Robert M Brosh
Apr 5, 2011·Mutation Research·Tae Moon KimPaul Hasty
Feb 7, 2015·Biochimica Et Biophysica Acta·Jill O FussJohn A Tainer
Jan 15, 2015·Biochimica Et Biophysica Acta·Viktoria Désirée Paul, Roland Lill
May 25, 2011·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Hiroyuki KitaoMinoru Takata
Nov 26, 2015·Human Genomics·Hongbin DongVasilis Vasiliou
Nov 7, 2014·Frontiers in Genetics·Robert M Brosh, Sharon B Cantor
Apr 25, 2016·Methods : a Companion to Methods in Enzymology·Manhong GuoYuliang Wu
Jul 5, 2016·Genes·Sanjay Kumar BhartiRobert M Brosh
Jan 23, 2016·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Haeyoung KimSeok Won Kim
Jun 20, 2017·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Ujala AymunShahida Mohsin
Sep 14, 2018·Cell Cycle·Srijita Dhar, Robert M Brosh
Jan 27, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zhi-Yin SunTian-Miao Ou
Mar 4, 2020·Genes·Robert M Brosh, Steven W Matson
Aug 19, 2014·Protein Science : a Publication of the Protein Society·Basudeb Bhattacharyya, James L Keck
Oct 12, 2017·Metallomics : Integrated Biometal Science·C WachnowskyJ A Cowan
Jul 13, 2018·Frontiers in Molecular Biosciences·Arindam Datta, Robert M Brosh
Dec 3, 2016·Biochemistry. Biokhimii︠a︡·Johnny StibanLaurie S Kaguni
Oct 9, 2020·Cold Spring Harbor Molecular Case Studies·Lara KamalMoien N Kanaan
Sep 30, 2020·Molecular and Cellular Biology·Jagadeesh Chandra Bose KSudit S Mukhopadhyay
Dec 12, 2019·Cancer Research·Cassandra L MoyerPaul J Goodfellow
Feb 18, 2021·Cell Chemical Biology·Pauline LejaultDavid Monchaud
Nov 3, 2020·DNA Repair·Srijita DharRobert M Brosh
Feb 24, 2021·Molecular Cancer Research : MCR·Jennifer A CalvoSharon B Cantor

❮ Previous
Next ❯

Related Concepts

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.