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Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation

Nature Cell Biology volume 2, pages 757–761 (2000)Cite this article

Abstract

Growth and development are dependent on the faithful duplication of cells. Duplication requires accurate genome replication, the repair of any DNA damage, and the precise segregation of chromosomes at mitosis; molecular checkpoints ensure the proper progression and fidelity of each stage. Loss of any of these highly conserved functions may result in genetic instability and proneness to cancer. Here we show that highly significant increases in chromosome missegregation occur in cell lines lacking the RAD51-like genes XRCC2 and XRCC3. This increased missegregation is associated with fragmentation of the centrosome, a component of the mitotic spindle, and not with loss of the spindle checkpoint. Our results show that unresolved DNA damage triggers this instability, and that XRCC2 and XRCC3 are potential tumour-suppressor genes in mammals.

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Figure 1: Karyotypic analysis of metaphase and interphase cells in irs1 (XRCC2-deficient) and irs1SF (XRCC3-deficient) lines.
Figure 2: Cell-cycle progression of irs1 (XRCC2-deficient) and V79 (parental line) cells in the presence of nocodazole.
Figure 3: Centrosome abnormalities and multipolar spindles in irs1 (XRCC2-deficient) and irs1SF (XRCC3-deficient) cells.

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Acknowledgements

We thank A. George, C. Tambini and S. Townsend for technical support, D. Papworth for statistical analysis, J. Savage for discussion, and T. Humphrey for comments on the manuscript. This work was supported by the European Commission (contract F14P-CT950010).

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  1. MRC Radiation & Genome Stability Unit, Harwell, OX11 0RD, Oxfordshire, England

    Carol S. Griffin, Paul J. Simpson, Caroline R. Wilson & John Thacker

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  1. Carol S. Griffin
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Correspondence to John Thacker.

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Griffin, C., Simpson, P., Wilson, C. et al. Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation. Nat Cell Biol 2, 757–761 (2000). https://doi.org/10.1038/35036399

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