Human Rif1, ortholog of a yeast telomeric protein, is regulated by ATM and 53BP1 and functions in the S-phase checkpoint

Genes & Development
Joshua SilvermanTitia de Lange

Abstract

We report on the function of the human ortholog of Saccharomyces cerevisiae Rif1 (Rap1-interacting factor 1). Yeast Rif1 associates with telomeres and regulates their length. In contrast, human Rif1 did not accumulate at functional telomeres, but localized to dysfunctional telomeres and to telomeric DNA clusters in ALT cells, a pattern of telomere association typical of DNA-damage-response factors. After induction of double-strand breaks (DSBs), Rif1 formed foci that colocalized with other DNA-damage-response factors. This response was strictly dependent on ATM (ataxia telangiectasia mutated) and 53BP1, but not affected by diminished function of ATR (ATM- and Rad3-related kinase), BRCA1, Chk2, Nbs1, and Mre11. Rif1 inhibition resulted in radiosensitivity and a defect in the intra-S-phase checkpoint. The S-phase checkpoint phenotype was independent of Nbs1 status, arguing that Rif1 and Nbs1 act in different pathways to inhibit DNA replication after DNA damage. These data reveal that human Rif1 contributes to the ATM-mediated protection against DNA damage and point to a remarkable difference in the primary function of this protein in yeast and mammals.

References

Dec 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·R B Painter, B R Young
Mar 14, 1995·Proceedings of the National Academy of Sciences of the United States of America·T HaafD C Ward
Feb 20, 1997·Nature·B van Steensel, T de Lange
Feb 26, 1998·Cell·B van SteenselT de Lange
Feb 26, 1999·Science·J KarlsederT de Lange
Jun 23, 1999·Mutation Research·M Kraakman-van der ZwetM Z Zdzienicka
Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·S M BaileyE H Goodwin
Feb 12, 2000·Molecular and Cellular Biology·A SmogorzewskaT de Lange
Dec 2, 2000·Nature·B B Zhou, S J Elledge
Dec 13, 2000·Molecular and Cellular Biology·O K Mirzoeva, J H Petrini
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·M B Kastan, D S Lim
Apr 21, 2001·Molecular and Cellular Biology·B XuM B Kastan
Aug 30, 2001·Current Biology : CB·S W ChanE H Blackburn
Sep 7, 2001·Genes & Development·R T Abraham
Nov 27, 2001·Science·D CortezS J Elledge
Jan 26, 2002·Molecular and Cellular Biology·Bo XuMichael B Kastan
Feb 19, 2002·Oncogene·Titia de Lange
Feb 19, 2002·Oncogene·Jeremy D HensonRoger R Reddel
Jun 4, 2002·Nature Medicine·Carl D NovinaPhillip A Sharp
Jun 28, 2002·Cell·Toshiyasu TaniguchiAlan D D'Andrea
Oct 4, 2002·Current Biology : CB·Agata SmogorzewskaTitia de Lange
Oct 5, 2002·Science·Bin WangStephen J Elledge
Nov 7, 2002·Cell·Shridar GanesanDavid M Livingston
Nov 26, 2002·Trends in Cell Biology·Alexander J OsbornLee Zou
Nov 26, 2002·Nature Cell Biology·Richard A DiTullioThanos D Halazonetis
Jan 2, 2003·Nature Reviews. Cancer·Alan D D'Andrea, Markus Grompe

❮ Previous
Next ❯

Citations

Jan 5, 2005·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Michele BrunoriVincent Géli
Jan 29, 2005·Nature Genetics·Woodring E Wright, Jerry W Shay
Sep 5, 2013·Nature Reviews. Molecular Cell Biology·Stephanie Panier, Daniel Durocher
Dec 12, 2013·Nature Reviews. Molecular Cell Biology·Stephanie Panier, Simon J Boulton
Jan 30, 2010·The Journal of Biological Chemistry·Sahn-Ho KimG Prem-Veer Reddy
Jun 2, 2009·Carcinogenesis·Haibo WangXingzhi Xu
Jan 27, 2012·Genes & Development·Motoshi HayanoHisao Masai
Jan 12, 2013·Science·Michela Di VirgilioMichel C Nussenzweig
Jan 12, 2013·Science·Michal ZimmermannTitia de Lange
Oct 31, 2008·Journal of Virology·Kevin NashNicholas Muzyczka
Dec 2, 2004·Molecular and Cellular Biology·Daniel L Levy, Elizabeth H Blackburn
Aug 19, 2005·Molecular and Cellular Biology·Eugene V ShakirovDorothy E Shippen
Nov 10, 2009·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Bettina A Moser, Toru M Nakamura
Aug 6, 2008·Annual Review of Genetics·Wilhelm Palm, Titia de Lange
Jun 21, 2012·BMC Genomics·Easwaran SreesankarKrishnaveni Mishra
Sep 2, 2006·Cell Division·Melissa M Adams, Phillip B Carpenter
Nov 19, 2008·Epigenetics & Chromatin·Christoffel DinantWim Vermeulen
Dec 24, 2011·PLoS Genetics·Yuan XueLaura Maringele
Dec 24, 2011·PLoS Genetics·Yaniv HarariMartin Kupiec
Jun 3, 2010·Frontiers in Bioscience (Landmark Edition)·Lakxmi Subramanian, Toru M Nakamura
Oct 8, 2013·Trends in Cell Biology·Michal Zimmermann, Titia de Lange
Oct 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Grant S StewartA Malcolm R Taylor
Jul 6, 2014·Nature Communications·Anne Fernandez-VidalJean-Sébastien Hoffmann
Oct 20, 2012·Journal of Molecular Neuroscience : MN·Sara L C EstevesEdgar F da Cruz e Silva
Mar 15, 2013·The Journal of Biological Chemistry·Lin FengJunjie Chen
Dec 2, 2009·The Journal of Cell Biology·Sara B C BuonomoTitia de Lange
Dec 8, 2004·The Journal of Cell Biology·Lifeng Xu, Elizabeth H Blackburn
Jan 20, 2016·Membranes·Joana B SerranoSandra Rebelo
May 27, 2009·The Journal of Cell Biology·Wei-Qin JiangRoger R Reddel
Jul 27, 2010·FEBS Letters·Sascha FeuerhahnJoachim Lingner
Jan 5, 2016·Molecular Cell·Rossana FotiSara C B Buonomo
Mar 9, 2011·Biochemical Pharmacology·Margarida FardilhaEdgar F da Cruz e Silva
Mar 30, 2010·Experimental Cell Research·S B C Buonomo
Mar 4, 2010·DNA Repair·Anastasia Zlatanou, Grant S Stewart
Aug 25, 2012·Chemical Research in Toxicology·Huiqi LiKarin Broberg
Oct 6, 2015·Nature Structural & Molecular Biology·Yutaka KanohHisao Masai

❮ Previous
Next ❯

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