Human FANCC is hypomorphic in murine Fancc-deficient cells

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

Research output: Contribution to journalArticle

7 Scopus citations

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

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Hays, L. E., Keeble, W. W., Yates, J. E., Rathbun, R. K., Koretsky, T., Olson, S. B., Sun, Z., Clapp, D. W., & 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