细胞分裂是一个至关重要的过程,其中一个重要步骤是复制遗传物质,被组织成称为染色体的结构。在一个细胞分裂成两个之前,它需要确保每个新复制的染色体与同卵双胞胎紧密配对。这种配对是由一种称为cohesin的蛋白质复合物维持的,在各种生物体中都是保守的,从单细胞到人类。Cohesin基本上包围了DNA,创建一个环状结构的手铐,将新合成的姐妹染色体成对保存在一起。因此,染色体内聚和分离是细胞分裂过程中控制姐妹染色单体附着和分离的基本过程。中期到后期的过渡需要通过酶分离酶溶解粘液素。这些过程的严格调节对于维护基因组稳定性至关重要。染色体内聚和分离失调导致非整倍性,一种以细胞染色体计数异常为特征的疾病,与癌症密切相关。非整倍体是许多癌症类型中反复出现的标志,染色体内聚和分离的异常已被确定为各种癌症的重要贡献者,比如急性髓细胞性白血病,骨髓增生异常综合征,结直肠,膀胱,和其他实体癌症。粘附分子复合物内的突变与这些癌症有关,因为它们干扰染色体分离,基因组组织,和基因表达,促进非整倍体并促进恶性肿瘤的发生。总之,染色体内聚和分离过程在保持基因组稳定性中起着关键作用,这些机制的畸变会导致非整倍性和癌症。对染色体内聚和分离的分子复杂性有更深入的了解,为在对抗癌症的斗争中开发创新的治疗方法提供了有希望的前景。
Cell division is a crucial process, and one of its essential steps involves copying the genetic material, which is organized into structures called chromosomes. Before a cell can divide into two, it needs to ensure that each newly copied chromosome is paired tightly with its identical twin. This pairing is maintained by a protein complex known as
cohesin, which is conserved in various organisms, from single-celled ones to humans.
Cohesin essentially encircles the DNA, creating a ring-like structure to handcuff, to keep the newly synthesized sister chromosomes together in pairs. Therefore, chromosomal cohesion and separation are fundamental processes governing the attachment and segregation of sister chromatids during cell division. Metaphase-to-anaphase transition requires dissolution of cohesins by the enzyme Separase. The tight regulation of these processes is vital for safeguarding genomic stability. Dysregulation in chromosomal cohesion and separation resulting in aneuploidy, a condition characterized by an abnormal chromosome count in a cell, is strongly associated with cancer. Aneuploidy is a recurring hallmark in many cancer types, and abnormalities in chromosomal cohesion and separation have been identified as significant contributors to various cancers, such as acute myeloid leukemia, myelodysplastic syndrome, colorectal, bladder, and other solid cancers. Mutations within the
cohesin complex have been associated with these cancers, as they interfere with chromosomal segregation, genome organization, and gene expression, promoting aneuploidy and contributing to the initiation of malignancy. In summary, chromosomal cohesion and separation processes play a pivotal role in preserving genomic stability, and aberrations in these mechanisms can lead to aneuploidy and cancer. Gaining a deeper understanding of the molecular intricacies of chromosomal cohesion and separation offers promising prospects for the development of innovative therapeutic approaches in the battle against cancer.