Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M

被引：107

作者：

Singh, Thiyam Ramsing ^{[2
]}

Bakker, Sietske T. ^{[1
,3
]}

Agarwal, Sheba ^{[1
]}

Jansen, Michael ^{[2
]}

Grassman, Elke ^{[2
]}

Godthelp, Barbara C. ^{[4
]}

Ali, Abdullah Mahmood ^{[2
]}

Du, Chang-hu ^{[2
]}

Rooimans, Martin A. ^{[1
]}

Fan, Qiang ^{[2
]}

Wahengbam, Kebola ^{[2
]}

Steltenpool, Jurgen ^{[1
]}

Andreassen, Paul R. ^{[2
]}

Williams, David A. ^{[2
]}

Joenje, Hans ^{[1
]}

de Winter, Johan P. ^{[1
]}

Meetei, Amom Ruhikanta ^{[2
]}

机构：

[1] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, NL-1081 BT Amsterdam, Netherlands

[2] Univ Cincinnati, Coll Med, Cincinnati Childrens Res Fdn, Div Expt Hematol & Canc Biol, Cincinnati, OH 45221 USA

[3] Netherlands Canc Inst, Div Mol Biol, NL-1066 CX Amsterdam, Netherlands

[4] Leiden Univ, Med Ctr, Dept Toxicogenet, Leiden, Netherlands

来源：

BLOOD | 2009年 / 114卷 / 01期

关键词：

CORE COMPLEX; PROTEIN; IDENTIFICATION; ORTHOLOG; HELICASE; HEF; RECOMBINATION; DEFICIENT; CHROMATIN; BRCA2;

D O I：

10.1182/blood-2009-02-207811

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

FANCM is a component of the Fanconi anemia ( FA) core complex and one FA patient (EUFA867) with biallelic mutations in FANCM has been described. Strikingly, we found that EUFA867 also carries biallelic mutations in FANCA. After correcting the FANCA defect in EUFA867 lymphoblasts, a "clean" FA-M cell line was generated. These cells were hypersensitive to mitomycin C, but unlike cells defective in other core complex members, FANCM(-/-) cells were proficient in monoubiquitinating FANCD2 and were sensitive to the topoisomerase inhibitor camptothecin, a feature shared only with the FA subtype D1 and N. In addition, FANCM(-/-) cells were sensitive to UV light. FANCM and a C-terminal deletion mutant rescued the cross-linker sensitivity of FANCM(-/-) cells, whereas a FANCM ATPase mutant did not. Because both mutants restored the formation of FANCD2 foci, we conclude that FANCM functions in an FA core complex dependent and -independent manner. (Blood. 2009; 114:174-180)

引用

页码：174 / 180

页数：7

共 33 条

[1] UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited independently to chromatin: A basis for the regulation of FANCD2 monoubiquitination [J].

Alpi, Arno ;

Langevin, Frederic ;

Mosedale, Georgina ;

Machida, Yuichi J. ;

Dutta, Anindya ;

Patel, Ketan J. .

MOLECULAR AND CELLULAR BIOLOGY, 2007, 27 (24) :8421-8430

[2] Genetic subtyping of Fanconi anemia by comprehensive mutation screening [J].

Ameziane, Najim ;

Errami, Abdellatif ;

Leveille, France ;

Fontaine, Chantal ;

de Vries, Yne ;

van Spaendonk, Rosalina M. L. ;

de Winter, Johan R. ;

Pals, Gerard ;

Joenje, Hans .

HUMAN MUTATION, 2008, 29 (01) :159-166

[3] Mph1p promotes gross chromosomal rearrangement through partial inhibition of homologous recombination [J].

Banerjee, Soma ;

Smith, Stephanie ;

Oum, Ji-Hyun ;

Liaw, Hung-Jiun ;

Hwang, Ji-Young ;

Sikdar, Nilabja ;

Motegi, Akira ;

Lee, Sang Eun ;

Myung, Kyungjae .

JOURNAL OF CELL BIOLOGY, 2008, 181 (07) :1083-1093

[4] A rapid method for retrovirus-mediated identification of complementation groups in Fanconi anemia patients [J].

Chandra, S ;

Levran, O ;

Jurickova, I ;

Maas, C ;

Kapur, R ;

Schindler, D ;

Henry, R ;

Milton, K ;

Batish, SD ;

Cancelas, JA ;

Hanenberg, H ;

Auerbach, AD ;

Williams, DA .

MOLECULAR THERAPY, 2005, 12 (05) :976-984

[5] Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM [J].

Ciccia, Alberto ;

Ling, Chen ;

Coulthard, Rachel ;

Yan, Zhijiang ;

Xue, Yutong ;

Meetei, Amom Ruhikanta ;

Laghmani, El Houari ;

Joenje, Hans ;

McDonald, Neil ;

de Winter, Johan P. ;

Wang, Weidong ;

West, Stephen C. .

MOLECULAR CELL, 2007, 25 (03) :331-343

[6] The genetic and molecular basis of Fanconi anemia [J].

de Winter, Johan P. ;

Joenje, Hans .

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2009, 668 (1-2) :11-19

[7] Remodeling of DNA replication structures by the branch point translocase FANCM [J].

Gari, Kerstin ;

Decaillet, Chantal ;

Delannoy, Mathieu ;

Wu, Leonard ;

Constantinou, Angelos .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (42) :16107-16112

[8] The Fanconi anemia protein FANCM can promote branch migration of Holliday junctions and replication forks [J].

Gari, Kerstin ;

Decaillet, Chantal ;

Stasiak, Alicjia Z. ;

Stasiak, Andrzej ;

Constantinou, Angelos .

MOLECULAR CELL, 2008, 29 (01) :141-148

[9] Inducibility of nuclear Rad51 foci after DNA damage distinguishes all Fanconi anemia complementation groups from D1/BRCA2 [J].

Godthelp, BC ;

Wiegant, WW ;

Waisfisz, Q ;

Medhurst, AL ;

Arwert, F ;

Joenje, H ;

Zdzienicka, MZ .

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2006, 594 (1-2) :39-48

[10] Biallelic inactivation of BRCA2 in Fanconi anemia [J].

Howlett, NG ;

Taniguchi, T ;

Olson, S ;

Cox, B ;

Waisfisz, Q ;

de Die-Smulders, C ;

Persky, N ;

Grompe, M ;

Joenje, H ;

Pals, G ;

Ikeda, H ;

Fox, EA ;

D'Andrea, AD .

SCIENCE, 2002, 297 (5581) :606-609

← 1 2 3 4 →