Lin Ho-Chen, Golic Mary M, Hill Hunter J, Lemons Katherine F, Vuong Truc T, Smith Madison, Golic Forrest, Golic Kent G
School of Biological Sciences, University of Utah, Salt Lake City, UT, USA.
bioRxiv. 2024 Aug 9:2024.08.08.607186. doi: 10.1101/2024.08.08.607186.
Ring chromosomes are known in many eukaryotic organisms, including humans. They are typically associated with a variety of maladies, including abnormal development and lethality. Underlying these phenotypes are anaphase chromatin bridges that can lead to chromosome loss, nondisjunction and breakage. By cytological examination of ring chromosomes in we identified five causes for anaphase bridges produced by ring chromosomes. Catenation of sister chromatids is the most common cause and these bridges frequently resolve during anaphase, presumably by the action of topoisomerase II. Sister chromatid exchange and chromosome breakage followed by sister chromatid union also produce anaphase bridges. Mitotic recombination with the homolog was rare, but was another route to generation of anaphase bridges. Most surprising, was the discovery of homolog capture, where the ring chromosome was connected to its linear homolog in anaphase. We hypothesize that this is a remnant of mitotic pairing and that the linear chromosome is connected to the ring by multiple wraps produced through the action of topoisomerase II during establishment of homolog pairing. In support, we showed that in a ring/ring homozygote the two rings are frequently catenated in mitotic metaphase, a configuration that requires breaking and rejoining of at least one chromosome.
环状染色体在包括人类在内的许多真核生物中都存在。它们通常与多种疾病相关,包括发育异常和致死性。这些表型的潜在原因是后期染色质桥,其可导致染色体丢失、不分离和断裂。通过对环状染色体的细胞学检查,我们确定了环状染色体产生后期桥的五个原因。姐妹染色单体连环是最常见的原因,这些桥在后期经常会解旋,推测是通过拓扑异构酶II的作用。姐妹染色单体交换和染色体断裂后姐妹染色单体结合也会产生后期桥。与同源染色体的有丝分裂重组很少见,但也是产生后期桥的另一条途径。最令人惊讶的是同源染色体捕获的发现,即环状染色体在后期与它的线性同源染色体相连。我们推测这是有丝分裂配对的残余物,并且线性染色体通过在同源染色体配对建立过程中拓扑异构酶II的作用产生的多个缠绕与环状染色体相连。作为支持,我们表明在环状/环状纯合子中,两个环在有丝分裂中期经常连环,这种构型需要至少一条染色体的断裂和重新连接。