Post-irradiation phosphorylation of structural maintenance chromosome 1 (SMC1) is independent of the Fanconi protein pathway.
OBJECTIVE
To confirm the sensitivity of cells from patients with Fanconi anemia (FA) to ionizing radiation, and to determine whether the phosphorylation of structural maintenance chromosome 1 (SMC1) was associated with radiosensitivity, as it is in other DNA repair disorders.


METHODS
Using lymphoblastoid cell lines from FA patients before and after exposure to ionizing radiation, the colony survival assay, radioresistant DNA synthesis, and SMC1 phosphorylation were measured. FA lymphoblastoid cell lines that had been transfected with the wild-type FANC gene were used as controls.


RESULTS
Cells from FA patients of six complementation groups were radiosensitive. Despite this, SMC1 phosphorylation was normal in each case; radioresistant DNA synthesis, a measure of S phase checkpoint integrity, was defective in FANCD2 lymphoblastoid cell lines and was corrected in FANCD2 + D2 cells.


CONCLUSIONS
The data indicate that the FANC pathway proteins play a major role in the cellular responses to ionizing radiation, but not in SMC1 phosphorylation or in the S phase checkpoint of FANCD2-deficient cells. Thus, SMC1 activation is not a common denominator of radiosensitivity, as has been suggested by radiation responses of cells from ataxia-telangiectasia, Nijmegen breakage syndrome, or Mre11 deficiency patients.
Nahas
Shareef A
SA
Department of Pathology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095-1732, USA.
Lai
Chih-Hung
CH
Gatti
Richard A
RA
D018797:Cell Cycle Proteins / Q000378:metabolism / Q000528:radiation effects*; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism / Q000528:radiation effects*; D004247:DNA / Q000096:biosynthesis / Q000528:radiation effects; D005199:Fanconi Anemia / Q000378:metabolism* / Q000473:pathology; D052236:Fanconi Anemia Complementation Group D2 Protein; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011836:Radiation Tolerance; D000098550:Structural Maintenance of Chromosome Protein 1
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; D009687:Nuclear Proteins; D000098550:Structural Maintenance of Chromosome Protein 1; D004247:DNA