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Ionizing radiation triggers chromatin-bound kin17 complex formation in human cells
Denis S F Biard1, Laurent Miccoli, Emmanuelle Despras
1Commissariat à l'Energie Atomique, Laboratoire de Génétique de la Radiosensibilité, Département de Radiobiologie et de Radiopathologie, Direction des Sciences du Vivant, Fontenay-aux-Roses 92265, France. biard@dsvidf.cea.fr
The Journal of Biological Chemistry
|March 7, 2002
Summary
The human DNA-binding kin17 protein associates with DNA and concentrates at damage sites after irradiation. Reduced kin17 levels impair cell growth and DNA replication, indicating its role in DNA maintenance.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The human DNA-binding kin17 protein (HSA)kin17 shows cross-reactivity with antibodies against E. coli RecA.
- RecA is a key protein in DNA repair and recombination pathways.
Purpose of the Study:
- To investigate the role of HSAkin17 in cellular response to DNA damage.
- To determine if HSAkin17 is involved in DNA maintenance and replication.
Main Methods:
- Cross-linking experiments on living cells to assess DNA association.
- Gamma irradiation of RKO cells followed by protein quantification and co-localization studies.
- Analysis of RKO cell clones with reduced HSAkin17 expression using antisense transcripts.
Main Results:
- HSAkin17 directly binds to chromosomal DNA.
- Gamma irradiation increases DNA-bound HSAkin17 levels, with protein concentrating in nucleoplasmic foci alongside replication protein A.
- Reduced HSAkin17 levels lead to decreased cell proliferation, clonogenic growth, and S-phase accumulation.
Conclusions:
- HSAkin17 is a DNA maintenance protein involved in the cellular response to DNA damage.
- HSAkin17 likely localizes to unrepaired DNA damage sites and aids in overcoming replication perturbations.