RAD21 (also known as KIAA0078, NXP1, HR21, Mcd1, Scc1, and hereafter called RAD21), an essential gene, encodes a DNA double-strand break (DSB) repair protein that is evolutionarily conserved in all eukaryotes from budding yeast to humans. RAD21 protein is a structural component of the highly conserved cohesin complex consisting of RAD21, SMC1a, SMC3, and SCC3 [STAG1 (SA1) and STAG2 (SA2) in metazoans] proteins, involved in sister chromatid cohesion. This function is essential for proper chromosome segregation, post-replicative DNA repair, and prevention of inappropriate recombination between repetitive regions. In interphase, cohesin also functions in the control of gene expression by binding to numerous sites within the genome. In addition to playing roles in the normal cell cycle and DNA DSB repair, RAD21 is also linked to the apoptotic pathways. Germline heterozygous or homozygous missense mutations in RAD21 have been associated with human genetic disorders, including developmental diseases such as Cornelia de Lange syndrome (CdLS) and chronic intestinal pseudo-obstruction (CIPO) called Mungan syndrome, respectively, and collectively termed as cohesinopathies. Somatic mutations and amplification of the RAD21 have also been widely reported in both human solid and hematopoietic tumors. Considering the role of RAD21 in a broad range of cellular processes that are hot spots in neoplasm, it is not surprising that the deregulation of RAD21 has been increasingly evident in human cancers. Herein, we review the biology of RAD21 and the cellular processes that this important protein regulates and discuss the significance of RAD21 deregulation in cancer and cohesinopathies.

RAD21（也称为KIAA0078 、NXP1、HR21、 Mcd1、Scc1 ，以下称为 RAD21）是一种必需基因，编码 DNA 双链断裂 (DSB) 修复蛋白，该蛋白在从发芽酵母到人类的所有真核生物中进化保守。RAD21 蛋白是由 RAD21、SMC1a、SMC3 和 SCC3 [后生动物中的 STAG1 (SA1) 和 STAG2 (SA2)] 蛋白组成的高度保守的 cohesin 复合物的结构成分，参与姐妹染色单体的内聚。此功能对于正确的染色体分离、复制后 DNA 修复和防止重复区域之间的不适当重组至关重要。在相间期，cohesin 还通过与基因组内的许多位点结合来控制基因表达。除了在正常细胞周期和 DNA DSB 修复中发挥作用外，RAD21 还与细胞凋亡途径有关。种系杂合或纯合错义突变RAD21与人类遗传疾病有关，包括发育疾病，例如 Cornelia de Lange 综合征 (CdLS) 和称为Mungan 综合征的慢性肠假性梗阻 (CIPO) ，统称为黏附病。RAD21 的体细胞突变和扩增也已在人类实体瘤和造血肿瘤中得到广泛报道。考虑到 RAD21 在作为肿瘤热点的广泛细胞过程中的作用，RAD21 的失调在人类癌症中越来越明显也就不足为奇了。在此，我们回顾了 RAD21 的生物学和这种重要蛋白质调节的细胞过程，并讨论了RAD21 的重要性 癌症和粘连蛋白的放松管制。