Griffin C S, Simpson P J, Wilson C R, Thacker J
MRC Radiation & Genome Stability Unit, Harwell, Oxfordshire OX11 0RD, England.
Nat Cell Biol. 2000 Oct;2(10):757-61. doi: 10.1038/35036399.
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.
生长和发育依赖于细胞的精确复制。复制需要准确的基因组复制、修复任何DNA损伤以及在有丝分裂时精确分离染色体；分子检查点确保每个阶段的正确进行和保真度。这些高度保守的功能中任何一项的丧失都可能导致基因不稳定和易患癌症。在这里，我们表明，在缺乏RAD51样基因XRCC2和XRCC3的细胞系中，染色体错分离显著增加。这种增加的错分离与中心体（有丝分裂纺锤体的一个组成部分）的碎片化有关，而与纺锤体检查点的丧失无关。我们的结果表明，未解决的DNA损伤引发了这种不稳定性，并且XRCC2和XRCC3是哺乳动物中的潜在肿瘤抑制基因。
