McDaniel Stephen L, Zweifel Erica, Harris Peter K W, Yao Meng-Chao, Cole Eric S, Chalker Douglas L
Department of Biology, Washington University in St. Louis, St Louis, MO 63130, USA.
Biology Department, St. Olaf College, 1520 St. Olaf Avenue, Northfield, MN 55057, USA.
Biol Open. 2016 Dec 15;5(12):1790-1798. doi: 10.1242/bio.021576.
The p68 DEAD box helicases comprise a widely conserved protein family involved in a large range of biological processes including transcription, splicing and translation. The genome of the ciliate Tetrahymena thermophile encodes two p68-like helicases, Drh1p and Lia2p. We show that DRH1 is essential for growth and completion of development. In growing cells, Drh1p is excluded from the nucleus and accumulates near cortical basal bodies. In contrast, during sexual reproduction, this protein localizes to meiotic micronuclei, initially in punctate foci in regions where centromeres and telomeres are known to reside and later in post-zygotic differentiating somatic macronuclei. Differentiation of the macronuclear genome involves extensive DNA rearrangements including fragmentation of the five pairs of germline-derived chromosomes into 180 chromosomal sub-fragments that are stabilized by de novo telomere deletion. In addition, thousands of internal eliminated sequences (IESs) are excised from loci dispersed throughout the genome. Strains with DRH1 deleted from the germline nuclei, which do not express the protein during post-zygotic development, fail to fragment the developing macronuclear chromosomes. IES excision still occurs in the absence of DRH1 zygotic expression; thus, Drh1p is the first protein found to be specifically required for chromosome breakage but not DNA elimination.
p68 DEAD盒解旋酶构成了一个广泛保守的蛋白质家族,参与包括转录、剪接和翻译在内的一系列生物过程。嗜热四膜虫的基因组编码两种p68样解旋酶,即Drh1p和Lia2p。我们发现DRH1对生长和发育的完成至关重要。在生长的细胞中,Drh1p被排除在细胞核外,并在皮质基体附近积累。相反,在有性生殖过程中,这种蛋白质定位于减数分裂微核,最初位于已知着丝粒和端粒所在区域的点状病灶中,随后定位于合子后分化的体细胞大核中。大核基因组的分化涉及广泛的DNA重排,包括将五对种系衍生的染色体片段化为180个染色体亚片段,这些亚片段通过从头端粒缺失而稳定。此外,数千个内部消除序列(IESs)从分散在整个基因组中的位点被切除。从种系核中删除DRH1的菌株,在合子后发育过程中不表达该蛋白质,无法使发育中的大核染色体片段化。在没有DRH1合子表达的情况下,IES切除仍然发生;因此,Drh1p是第一种被发现对染色体断裂而非DNA消除有特异性需求的蛋白质。