The DNA damage response (DDR) is necessary to maintain genome integrity and prevent the accumulation of oncogenic mutations. Consequently, proteins involved in the DDR often serve as tumor suppressors, carrying out the crucial task of keeping DNA fidelity intact. Mediator of DNA damage checkpoint 1 (MDC1) is a scaffold protein involved in the early steps of the DDR. MDC1 interacts directly with γ-H2AX, the phosphorylated form of H2AX, a commonly used marker for DNA damage. It then propagates the phosphorylation of H2AX by recruiting ATM kinase. While the function of MDC1 in the DDR has been reviewed previously, its role in cancer has not been reviewed, and numerous studies have recently identified a link between MDC1 and carcinogenesis. This includes MDC1 functioning as a tumor suppressor, with its loss serving as a biomarker for cancer and contributor to drug sensitivity. Studies also indicate that MDC1 operates outside of its traditional role in DDR, and functions as a co-regulator of nuclear receptor transcriptional activity, and that mutations in MDC1 are present in tumors and can also cause germline predisposition to cancer. This review will discuss reports that link MDC1 to cancer and identify MDC1 as an important player in tumor formation, progression, and treatment. We also discuss mechanisms by which MDC1 levels are regulated and how this contributes to tumor formation.

DNA 损伤反应 (DDR) 是维持基因组完整性和防止致癌突变积累所必需的。因此，参与 DDR 的蛋白质通常充当肿瘤抑制因子，执行保持 DNA 保真度完整的关键任务。DNA 损伤检查点 1 (MDC1) 的介质是参与 DDR 早期步骤的支架蛋白。MDC1 直接与 γ-H2AX 相互作用，γ-H2AX 是 H2AX 的磷酸化形式，是一种常用的 DNA 损伤标记物。然后它通过招募 ATM 激酶来传播 H2AX 的磷酸化。虽然 MDC1 在 DDR 中的功能之前已经过审查，但它在癌症中的作用尚未审查过，而且最近许多研究已经确定了 MDC1 与致癌作用之间的联系。这包括作为肿瘤抑制因子的 MDC1，其丧失作为癌症的生物标志物和药物敏感性的贡献者。研究还表明，MDC1 在其在 DDR 中的传统作用之外发挥作用，并作为核受体转录活性的共同调节剂起作用，并且 MDC1 中的突变存在于肿瘤中，也可能导致生殖细胞易患癌症。本综述将讨论将 MDC1 与癌症联系起来的报告，并将 MDC1 确定为肿瘤形成、进展和治疗的重要参与者。我们还讨论了 MDC1 水平的调节机制以及这如何促进肿瘤形成。并且 MDC1 的突变存在于肿瘤中，也会导致生殖系癌症易感性。本综述将讨论将 MDC1 与癌症联系起来的报告，并将 MDC1 确定为肿瘤形成、进展和治疗的重要参与者。我们还讨论了 MDC1 水平的调节机制以及这如何促进肿瘤形成。并且 MDC1 的突变存在于肿瘤中，也会导致生殖系癌症易感性。本综述将讨论将 MDC1 与癌症联系起来的报告，并将 MDC1 确定为肿瘤形成、进展和治疗的重要参与者。我们还讨论了 MDC1 水平的调节机制以及这如何促进肿瘤形成。