hCINAP regulates the DNA-damage response and mediates the resistance of acute myelocytic leukemia cells to therapy

• DOI: 10.1038/s41467-019-11795-5
• Publication Date: 2019-08-23T10:02:36Z
• Authors: Ruidan Xu; Shuyu Yu; Dan Zhu; Xinping Huang; Yuqi Xu; Yimin Lao; Yonglu Tian; Jinfang Zhang; Zefang Tang; Zemin Zhang; Jing Yi; Hong-Hu Zhu; Xiaofeng Zheng
• Keywords: Myelocytic leukemia

Acute myeloid leukemia (AML) is a genetically heterogeneous malignant disorder of the hematopoietic system, characterized by accumulation DNA-damaged immature precursors. Here, we find that hCINAP involved in repair double-stranded DNA breaks (DSB) and its expression correlates with AML prognosis. Following DSB, recruited to damage sites where it promotes SENP3-dependent deSUMOylation NPM1. This turn results dissociation RAP80 from site CTIP-dependent resection homologous recombination. NPM1 SUMOylation required for recruitment proteins at early stage DNA-damage response (DDR), SUMOylated impacts assembly BRCA1 complex. Knockdown also sensitizes patient-derived xenograft (PDX) mouse model chemotherapy. In clinical samples, low associated higher overall survival rate patients. These provide mechanistic insight into function during role resistance therapy.