Home LiteratureArticle Details
PMID: 15616572 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM.

The EMBO journal ·Vol. 24 ·No. 2 ·2005-01-26 ·Pages 418-27

Hirano S, Yamamoto K, Ishiai M, Yamazoe M, Seki M, Matsushita N, Ohzeki M, Yamashita YM, Arakawa H, Buerstedde JM, Enomoto T, Takeda S, Thompson LH, Takata M

Abstract

Some of the restarting events of stalled replication forks lead to sister chromatid exchange (SCE) as a result of homologous recombination (HR) repair with crossing over. The rate of SCE is elevated by the loss of BLM helicase or by a defect in translesion synthesis (TLS). We found that spontaneous SCE levels were elevated approximately 2-fold in chicken DT40 cells deficient in Fanconi anemia (FA) gene FANCC. To investigate the mechanism of the elevated SCE, we deleted FANCC in cells lacking Rad51 paralog XRCC3, TLS factor RAD18, or BLM. The increased SCE in fancc cells required Xrcc3, whereas the fancc/rad18 double mutant exhibited higher SCE than either single mutant. Unexpectedly, SCE in the fancc/blm mutant was similar to that in blm cells, indicating functional linkage between FANCC and BLM. Furthermore, MMC-induced formation of GFP-BLM nuclear foci was severely compromised in both human and chicken fancc or fancd2 cells. Our cell survival data suggest that the FA proteins serve to facilitate HR, but not global TLS, during crosslink repair.

MeSH Terms
Adenosine Triphosphatases/physiology Avian Proteins Blotting, Western Cell Cycle Proteins/physiology Cell Line DNA Helicases/physiology DNA Replication DNA-Binding Proteins/physiology Fanconi Anemia Complementation Group C Protein Fanconi Anemia Complementation Group Proteins Green Fluorescent Proteins/metabolism Humans Immunoprecipitation Nuclear Proteins/physiology Rad51 Recombinase RecQ Helicases Recombinant Fusion Proteins/metabolism Recombination, Genetic/genetics Reverse Transcriptase Polymerase Chain Reaction Sister Chromatid Exchange Ubiquitin-Protein Ligases
Chemicals
Avian Proteins Cell Cycle Proteins DNA-Binding Proteins FANCC protein, human Fanconi Anemia Complementation Group C Protein Fanconi Anemia Complementation Group Proteins Nuclear Proteins RAD18 protein, human Recombinant Fusion Proteins X-ray repair cross complementing protein 3 Green Fluorescent Proteins Ubiquitin-Protein Ligases RAD51 protein, Gallus gallus RAD51 protein, human Rad51 Recombinase Adenosine Triphosphatases Bloom syndrome protein DNA Helicases RecQ Helicases
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Hirano Seiki
Department of Immunology and Molecular Genetics, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Yamamoto Kazuhiko
Ishiai Masamichi
Yamazoe Mitsuyoshi
Seki Masayuki
Matsushita Nobuko
Ohzeki Mioko
Yamashita Yukiko M
Arakawa Hiroshi
Buerstedde Jean-Marie
Enomoto Takemi
Takeda Shunichi
Thompson Larry H
Takata Minoru
References (60)
60 references, click to expand
  1. Fanconi anemia group C protein prevents apoptosis in hematopoietic cells through redox regulation of GSTP1.
    Nat Med. 2001 Jul;7(7):814-20 PMID: 11433346
  2. Fanconi anemia proteins localize to chromatin and the nuclear matrix in a DNA damage- and cell cycle-regulated manner.
    J Biol Chem. 2001 Jun 29;276(26):23391-6 PMID: 11297559
  3. Fanconi anemia and DNA repair.
    Hum Mol Genet. 2001 Oct 1;10(20):2253-9 PMID: 11673408
  4. Recombinational DNA repair of damaged replication forks in Escherichia coli: questions.
    Annu Rev Genet. 2001;35:53-82 PMID: 11700277
  5. Recombination at double-strand breaks and DNA ends: conserved mechanisms from phage to humans.
    Mol Cell. 2001 Dec;8(6):1163-74 PMID: 11779493
  6. Cancer susceptibility and the functions of BRCA1 and BRCA2.
    Cell. 2002 Jan 25;108(2):171-82 PMID: 11832208
  7. FANCE: the link between Fanconi anaemia complex assembly and activity.
    EMBO J. 2002 Jul 1;21(13):3414-23 PMID: 12093742
  8. Biallelic inactivation of BRCA2 in Fanconi anemia.
    Science. 2002 Jul 26;297(5581):606-9 PMID: 12065746
  9. Interfaces between the detection, signaling, and repair of DNA damage.
    Science. 2002 Jul 26;297(5581):547-51 PMID: 12142523
  10. The C-terminal domain of the Bloom syndrome DNA helicase is essential for genomic stability.
    BMC Cell Biol. 2001;2:11 PMID: 11472631
  11. RAD18 and RAD54 cooperatively contribute to maintenance of genomic stability in vertebrate cells.
    EMBO J. 2002 Oct 15;21(20):5558-66 PMID: 12374756
  12. Nbs1 is essential for DNA repair by homologous recombination in higher vertebrate cells.
    Nature. 2002 Nov 7;420(6911):93-8 PMID: 12422221
  13. The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis.
    Hum Mol Genet. 2002 Dec 1;11(25):3135-44 PMID: 12444098
  14. Involvement of vertebrate polkappa in Rad18-independent postreplication repair of UV damage.
    J Biol Chem. 2002 Dec 13;277(50):48690-5 PMID: 12356753
  15. Regulation of the Fanconi anemia pathway by monoubiquitination.
    Semin Cancer Biol. 2003 Feb;13(1):77-82 PMID: 12507559
  16. The Fanconi anaemia/BRCA pathway.
    Nat Rev Cancer. 2003 Jan;3(1):23-34 PMID: 12509764
  17. RecQ helicases: caretakers of the genome.
    Nat Rev Cancer. 2003 Mar;3(3):169-78 PMID: 12612652
  18. A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome.
    Mol Cell Biol. 2003 May;23(10):3417-26 PMID: 12724401
  19. Molecular views of recombination proteins and their control.
    Nat Rev Mol Cell Biol. 2003 Jun;4(6):435-45 PMID: 12778123
  20. Multiple roles of Rev3, the catalytic subunit of polzeta in maintaining genome stability in vertebrates.
    EMBO J. 2003 Jun 16;22(12):3188-97 PMID: 12805232
  21. Fanconi anemia FANCG protein in mitigating radiation- and enzyme-induced DNA double-strand breaks by homologous recombination in vertebrate cells.
    Mol Cell Biol. 2003 Aug;23(15):5421-30 PMID: 12861027
  22. RecQ helicases: suppressors of tumorigenesis and premature aging.
    Biochem J. 2003 Sep 15;374(Pt 3):577-606 PMID: 12803543
  23. A novel ubiquitin ligase is deficient in Fanconi anemia.
    Nat Genet. 2003 Oct;35(2):165-70 PMID: 12973351
  24. The Bloom's syndrome helicase suppresses crossing over during homologous recombination.
    Nature. 2003 Dec 18;426(6968):870-4 PMID: 14685245
  25. Heterogeneity in Fanconi anemia: evidence for 2 new genetic subtypes.
    Blood. 2004 Apr 1;103(7):2498-503 PMID: 14630800
  26. Tracing the network connecting BRCA and Fanconi anaemia proteins.
    Nat Rev Cancer. 2004 Apr;4(4):266-76 PMID: 15057286
  27. Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage.
    Mol Cell. 2004 May 21;14(4):491-500 PMID: 15149598
  28. The Fanconi anaemia gene FANCC promotes homologous recombination and error-prone DNA repair.
    Mol Cell. 2004 Aug 27;15(4):607-20 PMID: 15327776
  29. Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination.
    EMBO J. 2004 Oct 1;23(19):3886-96 PMID: 15359278
  30. X-linked inheritance of Fanconi anemia complementation group B.
    Nat Genet. 2004 Nov;36(11):1219-24 PMID: 15502827
  31. A high susceptibility of Fanconi's anemia to chromosome breakage by DNA cross-linking agents.
    Cancer Res. 1973 Aug;33(8):1829-36 PMID: 4352739
  32. A manyfold increase in sister chromatid exchanges in Bloom's syndrome lymphocytes.
    Proc Natl Acad Sci U S A. 1974 Nov;71(11):4508-12 PMID: 4140506
  33. Is Fanconi's anaemia defective in a process essential to the repair of DNA cross links?
    Nature. 1975 Oct 9;257(5526):501-3 PMID: 1178054
  34. Hypomutability in Fanconi anemia cells is associated with increased deletion frequency at the HPRT locus.
    Proc Natl Acad Sci U S A. 1990 Nov;87(21):8383-7 PMID: 2236046
  35. Bloom syndrome: a mendelian prototype of somatic mutational disease.
    Medicine (Baltimore). 1993 Nov;72(6):393-406 PMID: 8231788
  36. The Bloom's syndrome gene product is homologous to RecQ helicases.
    Cell. 1995 Nov 17;83(4):655-66 PMID: 7585968
  37. Positional cloning of the Werner's syndrome gene.
    Science. 1996 Apr 12;272(5259):258-62 PMID: 8602509
  38. Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells.
    EMBO J. 1998 Sep 15;17(18):5497-508 PMID: 9736627
  39. Abnormal microsomal detoxification implicated in Fanconi anemia group C by interaction of the FAC protein with NADPH cytochrome P450 reductase.
    Blood. 1998 Nov 1;92(9):3050-6 PMID: 9787138
  40. Induction of the antigen receptor expression on B lymphocytes results in rapid competence for signaling of SLP-65 and Syk.
    EMBO J. 1998 Dec 15;17(24):7304-10 PMID: 9857187
  41. 300 million years of conserved synteny between chicken Z and human chromosome 9.
    Nat Genet. 1999 Mar;21(3):258-9 PMID: 10080173
  42. Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome.
    Nat Genet. 1999 May;22(1):82-4 PMID: 10319867
  43. Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae.
    Microbiol Mol Biol Rev. 1999 Jun;63(2):349-404 PMID: 10357855
  44. Sister chromatid exchanges are mediated by homologous recombination in vertebrate cells.
    Mol Cell Biol. 1999 Jul;19(7):5166-9 PMID: 10373565
  45. PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1.
    J Cell Biol. 1999 Oct 18;147(2):221-34 PMID: 10525530
  46. DNA cross-link repair protein SNM1A interacts with PIAS1 in nuclear focus formation.
    Mol Cell Biol. 2004 Dec;24(24):10733-41 PMID: 15572677
  47. Fanconi anemia protein FANCD2 promotes immunoglobulin gene conversion and DNA repair through a mechanism related to homologous recombination.
    Mol Cell Biol. 2005 Jan;25(1):34-43 PMID: 15601828
  48. How Fanconi anemia proteins promote the four Rs: replication, recombination, repair, and recovery.
    Environ Mol Mutagen. 2005 Mar-Apr;45(2-3):128-42 PMID: 15668941
  49. The importance of repairing stalled replication forks.
    Nature. 2000 Mar 2;404(6773):37-41 PMID: 10716434
  50. Mouse RAD54 affects DNA double-strand break repair and sister chromatid exchange.
    Mol Cell Biol. 2000 May;20(9):3147-56 PMID: 10757799
  51. BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures.
    Genes Dev. 2000 Apr 15;14(8):927-39 PMID: 10783165
  52. Sister chromatid gene conversion is a prominent double-strand break repair pathway in mammalian cells.
    EMBO J. 2000 Jul 3;19(13):3398-407 PMID: 10880452
  53. Possible association of BLM in decreasing DNA double strand breaks during DNA replication.
    EMBO J. 2000 Jul 3;19(13):3428-35 PMID: 10880455
  54. The Rad51 paralog Rad51B promotes homologous recombinational repair.
    Mol Cell Biol. 2000 Sep;20(17):6476-82 PMID: 10938124
  55. Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway.
    Mol Cell. 2001 Feb;7(2):249-62 PMID: 11239454
  56. Chromosome instability and defective recombinational repair in knockout mutants of the five Rad51 paralogs.
    Mol Cell Biol. 2001 Apr;21(8):2858-66 PMID: 11283264
  57. Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51.
    J Biol Chem. 2001 Jun 1;276(22):19375-81 PMID: 11278509
  58. The emerging genetic and molecular basis of Fanconi anaemia.
    Nat Rev Genet. 2001 Jun;2(6):446-57 PMID: 11389461
  59. Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability.
    Hum Mol Genet. 2001 Jun 1;10(12):1287-98 PMID: 11406610
  60. The N-terminal internal region of BLM is required for the formation of dots/rod-like structures which are associated with SUMO-1.
    Biochem Biophys Res Commun. 2001 Aug 17;286(2):322-7 PMID: 11500040
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600534
Published
2005-01-26
Epub
2004-00-23
Pages
418-27
Language
English
Region
England
NLM ID
8208664
PMCID
PMC545820
Subset
IM
Grants
NCI NIH HHS · R01 CA089405 · United States
NCI NIH HHS · CA89405 · United States
External Links
PubMed source DOI: 10.1038/sj.emboj.7600534 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2