Yusufzai Timur, Kadonaga James T
Section of Molecular Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Science. 2008 Oct 31;322(5902):748-50. doi: 10.1126/science.1161233.
DNA-dependent adenosine triphosphatases (ATPases) participate in a broad range of biological processes including transcription, DNA repair, and chromatin dynamics. Mutations in the HepA-related protein (HARP) ATPase are responsible for Schimke immuno-osseous dysplasia (SIOD), but the function of the protein is unknown. We found that HARP is an ATP-dependent annealing helicase that rewinds single-stranded DNA bubbles that are stably bound by replication protein A. Other related ATPases, including the DNA translocase Rad54, did not exhibit annealing helicase activity. Analysis of mutant HARP proteins suggests that SIOD is caused by a deficiency in annealing helicase activity. Moreover, the pleiotropy of HARP mutations is consistent with the function of HARP as an annealing helicase that acts throughout the genome to oppose the action of DNA-unwinding activities in the nucleus.
依赖DNA的三磷酸腺苷酶（ATP酶）参与广泛的生物过程，包括转录、DNA修复和染色质动力学。HepA相关蛋白（HARP）ATP酶的突变是导致施姆克免疫骨发育不良（SIOD）的原因，但该蛋白的功能尚不清楚。我们发现HARP是一种依赖ATP的退火解旋酶，它能使被复制蛋白A稳定结合的单链DNA气泡重新缠绕。其他相关的ATP酶，包括DNA转位酶Rad54，均未表现出退火解旋酶活性。对突变型HARP蛋白的分析表明，SIOD是由退火解旋酶活性缺陷引起的。此外，HARP突变的多效性与HARP作为一种退火解旋酶的功能一致，该酶在整个基因组中发挥作用，对抗细胞核中DNA解旋活性的作用。
