Kelley-Clarke Brenna, Ballestas Mary E, Komatsu Takashi, Kaye Kenneth M
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Ave., Boston, MA 02115, USA.
Virology. 2007 Jan 20;357(2):149-57. doi: 10.1016/j.virol.2006.07.052. Epub 2006 Sep 18.
The Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) tethers KSHV terminal repeat (TR) DNA to mitotic chromosomes to efficiently segregate episomes to progeny nuclei. LANA contains N- and C-terminal chromosome binding regions. We now show that C-terminal LANA preferentially concentrates to paired dots at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes through residues 996-1139. Deletions within C-terminal LANA abolished both self-association and chromosome binding, consistent with a requirement for self-association to bind chromosomes. A deletion abolishing TR DNA binding did not affect chromosome targeting, indicating LANA's localization is not due to binding its recognition sequence in chromosomal DNA. LANA distributed similarly on human and non-human mitotic chromosomes. These results are consistent with C-terminal LANA interacting with a cell factor that concentrates at pericentromeric and peri-telomeric regions of mitotic chromosomes.
卡波西肉瘤相关疱疹病毒（KSHV）潜伏相关核抗原（LANA）将KSHV末端重复序列（TR）DNA与有丝分裂染色体相连，以有效地将附加体分离到子代细胞核中。LANA包含N端和C端染色体结合区域。我们现在表明，C端LANA通过996 - 1139位残基优先聚集在有丝分裂染色体子集的着丝粒周围和端粒周围区域的配对点上。C端LANA内的缺失消除了自缔合和染色体结合，这与自缔合结合染色体的要求一致。消除TR DNA结合的缺失并不影响染色体靶向，表明LANA的定位不是由于其与染色体DNA中的识别序列结合。LANA在人类和非人类有丝分裂染色体上的分布相似。这些结果与C端LANA与一种集中在有丝分裂染色体着丝粒周围和端粒周围区域的细胞因子相互作用一致。
