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http://purl.uniprot.org/citations/21216274http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21216274http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Cell-cycle checkpoints guarantee movement through the cell cycle. Mitotic arrest deficiency 2 (Mad2), a mitotic checkpoint protein, appears crucial for generating the wait anaphase signal to prevent onset of anaphase. We evaluated effects of Mad2 haploinsufficiency on hematopoietic stem (HSC) and progenitor (HPC) function in response to stress.

Materials and methods

We studied effects of Mad2(+/-) on in vivo recovery of bone marrow HPC from cytotoxic effects and also effects of cytostatic agents on HPC growth in vitro using Mad2(+/-) mice.

Results

Mad2(+/-) HPCs were protected from cytotoxic effects in vivo of a cell-cycle-specific agent, Ara-C, events consistent with Mad2(+/-) HPCs being in a slow or noncycling state, but not from recovery of functional HPC after treatment with non-cycle-specific cyclophosphamide or sublethal irradiation. There were no differences in phenotyped HSCs in Mad2(+/-) &Mad2(+/+) mice, information confirmed by no changes in short- or long-term repopulating HSC assay. To better understand Mad2(+/-) HPC function, E3330, a cytostatic agent, was used to assess redox function of Ape1/Ref-1; colony growth was examined under 5% and 20% O(2) tension. Mad2(+/-) HPCs were less responsive to E3330 than Mad2(+/+) HPCs, and E3330 was more effective under lowered O(2) tension. Mad2(+/-) HPCs were not enhanced at lowered oxygen, as were Mad2(+/+) HPCs.

Conclusions

Our studies have unexpectedly found that Mad2 haploinsufficiency is protective in the presence of a cycle-specific DNA synthesis agent in vivo, and Ape1/Ref-1 inhibitor in vitro."xsd:string
http://purl.uniprot.org/citations/21216274http://purl.org/dc/terms/identifier"doi:10.1016/j.exphem.2010.12.012"xsd:string
http://purl.uniprot.org/citations/21216274http://purl.uniprot.org/core/author"Broxmeyer H.E."xsd:string
http://purl.uniprot.org/citations/21216274http://purl.uniprot.org/core/author"Kelley M.R."xsd:string
http://purl.uniprot.org/citations/21216274http://purl.uniprot.org/core/author"Hangoc G."xsd:string
http://purl.uniprot.org/citations/21216274http://purl.uniprot.org/core/author"Rohrabaugh S.L."xsd:string
http://purl.uniprot.org/citations/21216274http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21216274http://purl.uniprot.org/core/name"Exp Hematol"xsd:string
http://purl.uniprot.org/citations/21216274http://purl.uniprot.org/core/pages"415-423"xsd:string
http://purl.uniprot.org/citations/21216274http://purl.uniprot.org/core/title"Mad2 haploinsufficiency protects hematopoietic progenitor cells subjected to cell-cycle stress in vivo and to inhibition of redox function of Ape1/Ref-1 in vitro."xsd:string
http://purl.uniprot.org/citations/21216274http://purl.uniprot.org/core/volume"39"xsd:string
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