Rocheteau Pierre, Tajbakhsh Shahragim
Cellules Souches et Développement, Département de Biologie du Développement, Institut Pasteur, CNRS URA 2578, 25, rue du Docteur Roux, 75724 Paris Cedex 15, France.
Med Sci (Paris). 2008 Oct;24(10):847-52. doi: 10.1051/medsci/20082410847.
During mitosis each daughter cell inherits a full copy of the maternal genomic material. DNA replication, however, is an imprecise process, thus errors can arise resulting in potentially deleterious mutations over extended rounds of cell division and these may lead to cancinogenesis. Over thirty years ago, J. Cairns proposed that a cell could avoid the accumulation of mutations arising from DNA replication if all template DNA strands are inherited in one daughter cell during cell division, thus giving rise to the notion of << immortal >> DNA strands. In this model the stem cells would retain the template DNA (older) strands. Proving or disproving this notion experimentally has been challenging. Further, it has recently become apparent that epigenetic regulation of gene expression plays a critical role in governing cell states, self-renewal and differentiation. In light of these data, can the phenomenon on template DNA strand segregation also reflect this epigenetic signature? In this review we explore these notions, discuss the evidence in support of this theory, the implications, and some of the mechanisms which could explain this phenomenon.
在有丝分裂过程中,每个子细胞继承母本基因组物质的完整拷贝。然而,DNA复制是一个不精确的过程,因此可能会出现错误,在细胞分裂的多轮过程中导致潜在的有害突变,而这些突变可能会引发癌症。三十多年前,J. 凯恩斯提出,如果在细胞分裂过程中所有模板DNA链都被一个子细胞继承,那么细胞可以避免因DNA复制而产生的突变积累,从而产生了“不朽”DNA链的概念。在这个模型中,干细胞将保留模板DNA(较旧的)链。通过实验证明或反驳这一概念一直具有挑战性。此外,最近很明显,基因表达的表观遗传调控在控制细胞状态、自我更新和分化方面起着关键作用。鉴于这些数据,模板DNA链分离现象是否也能反映这种表观遗传特征呢?在这篇综述中,我们探讨这些概念,讨论支持这一理论的证据、其影响以及一些可以解释这一现象的机制。