MORC2（一种染色质重塑 ATP 酶）的特征尚不明确，其变体会导致表观遗传调控和 DNA 损伤反应的缺陷。 MORC2 的 C 末端结构域 (CTD) 在 DNA 损伤中经常被磷酸化，可促进癌症进展，但其在染色质重塑中的作用仍不清楚。在这里，我们报告了全长磷酸化 MORC2 的分子特征，证明了它对结合开放染色质的偏好并发挥 DNA 滑动夹的作用。我们在 CTD 内发现了一个磷酸盐相互作用基序，它决定了 ATP 水解速率和协同 DNA 结合。 DNA 结合影响 ATP 酶区域内的多个结构域。我们提供了第一个视觉证据，证明 MORC2 通过 ATP 水解依赖性 DNA 压缩诱导染色质重塑，并受其磷酸化状态的调节。这些发现强调 MORC2 CTD 的磷酸化是染色质重塑的关键调节剂，使其成为潜在的治疗靶点。

Variants in the poorly characterised oncoprotein, MORC2, a chromatin remodelling ATPase, lead to defects in epigenetic regulation and DNA damage response. The C-terminal domain (CTD) of MORC2, frequently phosphorylated in DNA damage, promotes cancer progression, but its role in chromatin remodelling remains unclear. Here, we report a molecular characterisation of full-length, phosphorylated MORC2, demonstrating its preference for binding open chromatin and functioning as a DNA sliding clamp. We identified a phosphate interacting motif within the CTD that dictates ATP hydrolysis rate and cooperative DNA binding. The DNA binding impacts several structural domains within the ATPase region. We provide the first visual proof that MORC2 induces chromatin remodelling through ATP hydrolysis-dependent DNA compaction, regulated by its phosphorylation state. These findings highlight phosphorylation of MORC2 CTD as a key modulator of chromatin remodelling, presenting it as a potential therapeutic target.