XRCC1–DNA polymerase ß interaction is required for efficient base excision repair.

Sleeth, Kate M. and Dianova, Irina I. and Allinson, Sarah L. and Parsons, Jason L. and Breslin, Claire and Caldecott, Keith W. and Dianov, Grigory L. (2004) XRCC1–DNA polymerase ß interaction is required for efficient base excision repair. Nucleic Acids Research, 32 (8). pp. 2550-2555. ISSN 0305-1048

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Abstract

X-ray repair cross-complementing protein-1 (XRCC1)-deficient cells are sensitive to DNA damaging agents and have delayed processing of DNA base lesions. In support of its role in base excision repair, it was found that XRCC1 forms a tight complex with DNA ligase III and also interacts with DNA polymerase ß (Pol ß) and other base excision repair (BER) proteins. We have isolated wild-type XRCC1–DNA ligase III heterodimer and mutated XRCC1–DNA ligase III complex that does not interact with Pol ß and tested their activities in BER reconstituted with human purified proteins. We find that a point mutation in the XRCC1 protein which disrupts functional interaction with Pol ß, affected the ligation efficiency of the mutant XRCC1–DNA ligase III heterodimer in reconstituted BER reactions. We also compared sensitivity to hydrogen peroxide between wild-type CHO-9 cells, XRCC1-deficient EM-C11 cells and EM-C11 cells transfected with empty plasmid vector or with plasmid vector carrying wild-type or mutant XRCC1 gene and find that the plasmid encoding XRCC1 protein, that does not interact with Pol ß has reduced ability to rescue the hydrogen peroxide sensitivity of XRCC1- deficient cells. These data suggest an important role for the XRCC1–Pol ß interaction for coordinating the efficiency of the BER process.

Item Type:
Journal Article
Journal or Publication Title:
Nucleic Acids Research
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300/1311
Subjects:
?? geneticsqh301 biology ??
ID Code:
10159
Deposited By:
Deposited On:
08 Jul 2008 12:06
Refereed?:
Yes
Published?:
Published
Last Modified:
15 Jul 2024 09:12