Human FANCC is hypomorphic in murine Fancc-deficient cells

Laura E. Hays, Winifred W. Keeble, Jane E. Yates, R. K. Rathbun, Tara Koretsky, Susan Olson, Zejin Sun, D. Wade Clapp, Grover C. Bagby

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Fancc suppresses cross-linker-induced genotoxicity, modulates growth-inhibitory cytokine responses, and modulates endotoxin responses. Although loss of the latter function is known to account for endotoxin-induced marrow failure in murine Fancc (mFancc)-deficient mice, some argue that cytokine and endotoxin hypersensitivities devolve simply from genomic instability. Seeking to resolve this question, we planned to ectopically express instructive human FANCC(hFANCC) mutants in murine Fancc-deficient hematopoietic stem cells. To first assure that hFANCC cDNA was competent in murine cells, we compared hFANCC and mFancc in complementation assays for cross-linking agent hypersensitivity and endotoxin hypersensitivity. We found that mFancc complemented murine Fancc-deficient cells in both assays, but that hFANCC fully suppressed only endotoxin hypersensitivity, not cross-linking agent hypersensitivity. These results support the notions that Fancc is multifunctional and that structural prerequisites for its genoprotective functions differ from those required to constrain endotoxin responses known to lead to marrow failure in Fancc-deficient mice.

Original languageEnglish (US)
Pages (from-to)2057-2060
Number of pages4
JournalBlood
Volume116
Issue number12
DOIs
StatePublished - Sep 23 2010

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Endotoxins
Hypersensitivity
Assays
Bone Marrow
Cytokines
Genomic Instability
Hematopoietic Stem Cells
Stem cells
Complementary DNA
Growth

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology
  • Medicine(all)

Cite this

Hays, L. E., Keeble, W. W., Yates, J. E., Rathbun, R. K., Koretsky, T., Olson, S., ... Bagby, G. C. (2010). Human FANCC is hypomorphic in murine Fancc-deficient cells. Blood, 116(12), 2057-2060. https://doi.org/10.1182/blood-2010-02-266411

Human FANCC is hypomorphic in murine Fancc-deficient cells. / Hays, Laura E.; Keeble, Winifred W.; Yates, Jane E.; Rathbun, R. K.; Koretsky, Tara; Olson, Susan; Sun, Zejin; Clapp, D. Wade; Bagby, Grover C.

In: Blood, Vol. 116, No. 12, 23.09.2010, p. 2057-2060.

Research output: Contribution to journalArticle

Hays, LE, Keeble, WW, Yates, JE, Rathbun, RK, Koretsky, T, Olson, S, Sun, Z, Clapp, DW & Bagby, GC 2010, 'Human FANCC is hypomorphic in murine Fancc-deficient cells', Blood, vol. 116, no. 12, pp. 2057-2060. https://doi.org/10.1182/blood-2010-02-266411
Hays LE, Keeble WW, Yates JE, Rathbun RK, Koretsky T, Olson S et al. Human FANCC is hypomorphic in murine Fancc-deficient cells. Blood. 2010 Sep 23;116(12):2057-2060. https://doi.org/10.1182/blood-2010-02-266411
Hays, Laura E. ; Keeble, Winifred W. ; Yates, Jane E. ; Rathbun, R. K. ; Koretsky, Tara ; Olson, Susan ; Sun, Zejin ; Clapp, D. Wade ; Bagby, Grover C. / Human FANCC is hypomorphic in murine Fancc-deficient cells. In: Blood. 2010 ; Vol. 116, No. 12. pp. 2057-2060.
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