Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Instituto Nacional de Cancerología, Mexico.
Mutat Res. 2010 Dec;705(3):246-51. doi: 10.1016/j.mrrev.2010.09.002. Epub 2010 Oct 20.
Chromosomal instability (CIN) involves the gain or loss of complete or partial chromosomes during cellular division, and it is a common characteristic of tumors that have aneuploidy. In addition, CIN is considered to be a closely related event to carcinogenesis. The mechanisms that lead to CIN include defects in the cohesion of sister chromatids, mitotic spindle checkpoint, and regulation of the number of centrosomes. Different studies have found that transcription variants, also known as isoforms, which are generated by the alternative splicing of exons and introns in mRNA that encodes many of the regulator proteins of chromosomal segregation, have an important role in mechanisms that lead to CIN. The majority of these isoforms are newly described. The discovery of additional isoforms and the study of their mechanisms of action allow a more integrated view of how cells regulate the segregation of their genetic material, and of how errors occur in chromosomal segregation.
染色体不稳定性(CIN)涉及在细胞分裂过程中完整或部分染色体的获得或丢失,并且是具有非整倍体的肿瘤的常见特征。此外,CIN 被认为是与癌变密切相关的事件。导致 CIN 的机制包括姐妹染色单体的内聚力缺陷、有丝分裂纺锤体检查点和中心体数量的调节。不同的研究发现,转录变体,也称为同工型,是由编码染色体分离调节剂蛋白的 mRNA 中外显子和内含子的选择性剪接产生的,在导致 CIN 的机制中具有重要作用。这些同工型中的大多数都是新描述的。额外同工型的发现和对其作用机制的研究允许更全面地了解细胞如何调节其遗传物质的分离,以及染色体分离中错误是如何发生的。