The MCM8/9 complex is implicated in aiding fork progression and facilitating homologous recombination (HR) in response to several DNA damage agents. MCM9 itself is an outlier within the MCM family containing a long C-terminal extension (CTE) comprising 42% of the total length, but with no known functional components and high predicted disorder. In this report, we identify and characterize two unique motifs within the primarily unstructured CTE that are required for localization of MCM8/9 to sites of mitomycin C (MMC) induced DNA damage. First, an unconventional bipartite-like nuclear localization (NLS) motif consisting of two positively charged amino acid stretches separated by a long intervening sequence is required for the nuclear import of both MCM8 and MCM9. Second, a variant of the BRC motif (BRCv), similar to that found in other HR helicases, is necessary for localization to sites of MMC damage. The MCM9-BRCv directly interacts with and recruits RAD51 downstream to MMC-induced damage to aid in DNA repair. Patient lymphocytes devoid of functional MCM9 and discrete MCM9 knockout cells have a significantly impaired ability to form RAD51 foci after MMC treatment. Therefore, the disordered CTE in MCM9 is functionally important in promoting MCM8/9 activity and in recruiting downstream interactors; thus, requiring full length MCM9 for proper DNA repair.

中文翻译：

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MCM9的C末端域的母题直接定位到丝裂霉素C损伤的RAD51招聘网站。

MCM8 / 9复合物与叉的进展有关，并有助于对几种DNA损伤剂的同源重组（HR）。MCM9本身是MCM家族中的一个异常值，包含一个长的C末端延伸（CTE），占总长度的42％，但没有已知的功能组件和较高的预测障碍。在本报告中，我们鉴定并鉴定了MCM8 / 9定位到丝裂霉素C（MMC）诱导的DNA损伤位点所需的主要非结构化CTE中的两个独特基序。首先，MCM8和MCM9的核输入都需要一个非常规的两方样核定位（NLS）基序，该基序由两个带正电荷的氨基酸序列（由一个长的插入序列分隔）组成。其次，BRC基序（BRCv）的变体，与其他HR解旋酶中的变体相似，是定位到MMC损坏站点所必需的。MCM9-BRCv与MMC诱导的损伤直接相互作用并向下游募集RAD51，以协助DNA修复。缺乏功能性MCM9和离散MCM9敲除细胞的患者淋巴细胞在MMC治疗后形成RAD51灶的能力明显受损。因此，MCM9中无序的CTE在促进MCM8 / 9活性和募集下游相互作用因子方面具有重要的功能。因此，需要全长MCM9才能正确修复DNA。MCM9中无序的CTE在促进MCM8 / 9活性和募集下游相互作用因子方面具有重要的功能；因此，需要全长MCM9才能正确修复DNA。MCM9中无序的CTE在促进MCM8 / 9活性和募集下游相互作用因子方面具有重要的功能；因此，需要全长MCM9才能正确修复DNA。