别名 DNA polymerase alpha 1, catalytic subunit、DNA polymerase alpha catalytic subunit、DNA polymerase alpha catalytic subunit p180 + [7] |
简介 Catalytic subunit of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which plays an essential role in the initiation of DNA synthesis. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, a regulatory subunit POLA2 and two primase subunits PRIM1 and PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes. In the cytosol, responsible for a substantial proportion of the physiological concentration of cytosolic RNA:DNA hybrids, which are necessary to prevent spontaneous activation of type I interferon responses (PubMed:27019227). |
靶点 |
作用机制 POLA1抑制剂 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段批准上市 |
首次获批国家/地区 美国 |
首次获批日期2005-10-28 |
作用机制 POLA1抑制剂 [+3] |
原研机构 |
最高研发阶段批准上市 |
首次获批国家/地区 美国 |
首次获批日期2004-12-28 |
作用机制 HDAC11抑制剂 [+1] |
在研适应症 |
非在研适应症- |
最高研发阶段临床前 |
首次获批国家/地区- |
首次获批日期1800-01-20 |
开始日期2024-11-01 |
申办/合作机构 |
开始日期2024-08-09 |
申办/合作机构 |
开始日期2024-07-18 |
申办/合作机构 |