Journal ArticleDOI
Mutation of the RAD51C gene in a Fanconi anemia-like disorder
Fiona Vaz,Helmut Hanenberg,Helmut Hanenberg,Beatrice Schuster,Karen Barker,Constanze Wiek,Verena Erven,Kornelia Neveling,Daniela Endt,Ian Kesterton,Flavia Autore,Franca Fraternali,Marcel Freund,Linda Hartmann,David Grimwade,Roland G. Roberts,Heiner Schaal,Shehla Mohammed,Nazneen Rahman,Detlev Schindler,Christopher G. Mathew +20 more
TLDR
Biallelic germline mutations in a RAD51 paralog are associated with an FA-like syndrome because of loss of RAD51 focus formation in response to DNA damage and in increased cellular sensitivity to the DNA interstrand cross-linking agent mitomycin C and the topoisomerase-1 inhibitor camptothecin.Abstract:
Fanconi anemia (FA) is a rare chromosomal-instability disorder associated with a variety of developmental abnormalities, bone marrow failure and predisposition to leukemia and other cancers. We have identified a homozygous missense mutation in the RAD51C gene in a consanguineous family with multiple severe congenital abnormalities characteristic of FA. RAD51C is a member of the RAD51-like gene family involved in homologous recombination-mediated DNA repair. The mutation results in loss of RAD51 focus formation in response to DNA damage and in increased cellular sensitivity to the DNA interstrand cross-linking agent mitomycin C and the topoisomerase-1 inhibitor camptothecin. Thus, biallelic germline mutations in a RAD51 paralog are associated with an FA-like syndrome.read more
Citations
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Journal ArticleDOI
DNA interstrand crosslink repair and cancer.
Andrew J. Deans,Stephen C. West +1 more
TL;DR: Understanding how the FA pathway links nucleases, helicases and other DNA-processing enzymes should lead to more targeted uses of ICL-inducing agents in cancer treatment and could provide novel insights into drug resistance.
Journal ArticleDOI
RAD51B in Familial Breast Cancer
Liisa M. Pelttari,Sofia Khan,Mikko Vuorela,Johanna I. Kiiski,Sara Vilske,Viivi Nevanlinna,Salla Ranta,Johanna Schleutker,Johanna Schleutker,Johanna Schleutker,Robert Winqvist,Anne Kallioniemi,Thilo Dörk,Natalia Bogdanova,Jonine Figueroa,Paul D.P. Pharoah,Marjanka K. Schmidt,Alison M. Dunning,Montserrat Garcia-Closas,Manjeet K. Bolla,Joe Dennis,Kyriaki Michailidou,Qin Wang,John L. Hopper,Melissa C. Southey,Efraim H. Rosenberg,Peter A. Fasching,Peter A. Fasching,Matthias W. Beckmann,Julian Peto,Isabel dos-Santos-Silva,Elinor J. Sawyer,Ian Tomlinson,Barbara Burwinkel,Barbara Burwinkel,Harald Surowy,Harald Surowy,Pascal Guénel,Thérèse Truong,Stig E. Bojesen,Stig E. Bojesen,Børge G. Nordestgaard,Børge G. Nordestgaard,Javier Benitez,Anna González-Neira,Susan L. Neuhausen,Hoda Anton-Culver,Hermann Brenner,Volker Arndt,Alfons Meindl,Rita K. Schmutzler,Hiltrud Brauch,Hiltrud Brauch,Hiltrud Brauch,Thomas Brüning,Annika Lindblom,Sara Margolin,Arto Mannermaa,Jaana M. Hartikainen,Georgia Chenevix-Trench,kConFab,kConFab,Aocs Investigators,Laurien Van Dyck,Hilde Janssen,Hilde Janssen,Jenny Chang-Claude,Anja Rudolph,Paolo Radice,Paolo Peterlongo,Emily Hallberg,Janet E. Olson,Janet E. Olson,Graham G. Giles,Graham G. Giles,Roger L. Milne,Christopher A. Haiman,Fredrick Schumacher,Jacques Simard,Martine Dumont,Martine Dumont,Vessela N. Kristensen,Vessela N. Kristensen,Anne Lise Børresen-Dale,Wei Zheng,Alicia Beeghly-Fadiel,Mervi Grip,Mervi Grip,Irene L. Andrulis,Gord Glendon,Peter Devilee,Caroline Seynaeve,Maartje J. Hooning,Margriet Collée,Angela Cox,Simon S. Cross,Mitul Shah,Robert Luben,Ute Hamann,Ute Hamann,Diana Torres,Anna Jakubowska,Jan Lubinski,Fergus J. Couch,Drakoulis Yannoukakos,Nick Orr,Anthony J. Swerdlow,Hatef Darabi,Jingmei Li,Kamila Czene,Per Hall,Douglas F. Easton,Johanna Mattson,Carl Blomqvist,Kristiina Aittomäki,Heli Nevanlinna +115 more
TL;DR: It is suggested that loss-of-function mutations in RAD 51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.
Journal ArticleDOI
Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene
Alfons Meindl,Heide Hellebrand,Constanze Wiek,Verena Erven,Barbara Wappenschmidt,Dieter Niederacher,Marcel Freund,Peter Lichtner,Linda Hartmann,Heiner Schaal,Juliane Ramser,Ellen Honisch,Christian Kubisch,Hans Erich Wichmann,Karin Kast,Helmut Deissler,Christoph Engel,Bertram Müller-Myhsok,Kornelia Neveling,Marion Kiechle,Christopher G. Mathew,Detlev Schindler,Rita K. Schmutzler,Helmut Hanenberg,Helmut Hanenberg +24 more
TL;DR: In index cases from 1,100 German families with gynecological malignancies, the first unambiguous evidence of highly penetrant mutations associated with human cancer in a RAD51 paralog is provided and support the 'common disease, rare allele' hypothesis.
Journal ArticleDOI
Homologous Recombination and Human Health: The Roles of BRCA1, BRCA2, and Associated Proteins
TL;DR: This review summarizes recent findings on BRCA1, BRCa2, and associated proteins involved in human disease with an emphasis on their molecular roles and interactions.
Journal ArticleDOI
Homologous recombination and its regulation
TL;DR: Since mutations in several proteins that regulate Rad51 nucleofilaments are associated with cancer and cancer-prone syndromes, it is discussed how understanding their functions can lead to the development of better tools for cancer diagnosis and therapy.
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Journal ArticleDOI
Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene
Alfons Meindl,Heide Hellebrand,Constanze Wiek,Verena Erven,Barbara Wappenschmidt,Dieter Niederacher,Marcel Freund,Peter Lichtner,Linda Hartmann,Heiner Schaal,Juliane Ramser,Ellen Honisch,Christian Kubisch,Hans Erich Wichmann,Karin Kast,Helmut Deissler,Christoph Engel,Bertram Müller-Myhsok,Kornelia Neveling,Marion Kiechle,Christopher G. Mathew,Detlev Schindler,Rita K. Schmutzler,Helmut Hanenberg,Helmut Hanenberg +24 more
TL;DR: In index cases from 1,100 German families with gynecological malignancies, the first unambiguous evidence of highly penetrant mutations associated with human cancer in a RAD51 paralog is provided and support the 'common disease, rare allele' hypothesis.
Journal ArticleDOI
Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer
Sarah Reid,Detlev Schindler,Helmut Hanenberg,Helmut Hanenberg,Karen Barker,Sandra Hanks,Reinhard Kalb,Kornelia Neveling,Patrick Kelly,Sheila Seal,Marcel Freund,Melanie Wurm,Sat Dev Batish,Sat Dev Batish,Francis P. Lach,Sevgi Yetgin,Heidemarie Neitzel,Hany Ariffin,Marc Tischkowitz,Marc Tischkowitz,Christopher G. Mathew,Arleen D. Auerbach,Nazneen Rahman +22 more
TL;DR: It is demonstrated that biallelic PALB2 mutations cause a new subtype of Fanconi anemia, FA-N, and, similar to bIALlelic BRCA2 mutations, confer a high risk of childhood cancer.
Journal ArticleDOI
Colocalization of retrovirus and target cells on specific fibronectin fragments increases genetic transduction of mammalian cells.
Helmut Hanenberg,Xiang Li Xiao,Dagmar Dilloo,Kimikazu Hashino,Ikunoshin Kato,David R. Williams +5 more
TL;DR: It is demonstrated that enhanced gene transfer into mammalian target cells is due to direct binding of retroviral particles to sequences within the fibronectin molecule.
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