Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
J Biol Chem. 2013 Mar 1;288(9):6342-50. doi: 10.1074/jbc.M112.411603. Epub 2013 Jan 16.
Alpha thalassemia/mental retardation syndrome X-linked (ATRX) is a member of the SWI/SNF protein family of DNA-dependent ATPases. It functions as a chromatin remodeler and is classified as an SNF2-like helicase. Here, we showed somatic knock-out of ATRX displayed perturbed S-phase progression as well as hypersensitivity to replication stress. ATRX is recruited to sites of DNA damage, required for efficient checkpoint activation and faithful replication restart. In addition, we identified ATRX as a binding partner of MRE11-RAD50-NBS1 (MRN) complex. Together, these results suggest a non-canonical function of ATRX in guarding genomic stability.
X 连锁α地中海贫血/智力迟钝综合征（ATRX）是 DNA 依赖性 ATP 酶 SWI/SNF 蛋白家族的成员。它作为染色质重塑因子发挥作用，并被归类为 SNF2 样解旋酶。在这里，我们显示出体细胞敲除 ATRX 显示出 S 期进展受到干扰，以及对复制应激的过度敏感。ATRX 被募集到 DNA 损伤部位，这对于有效激活检查点和忠实复制启动是必需的。此外，我们还鉴定出 ATRX 是 MRE11-RAD50-NBS1（MRN）复合物的结合伴侣。总之，这些结果表明 ATRX 在保护基因组稳定性方面具有非典型功能。
