Rodemoyer Brian, Kariyawasam Ganesha, Subramanian Veena, Schmidt Kristina
Department of Molecular Biosciences, University of South Florida, 4202 E. Fowler Ave., Tampa, FL, 33620, USA.
Cancer Biology & Evolution Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.
Commun Biol. 2025 Mar 25;8(1):492. doi: 10.1038/s42003-025-07916-0.
Vertebrates possess two condensins, I and II, that are essential for chromosome condensation and segregation. Condensin II has also been implicated in maintaining genome integrity outside of mitosis, though the underlying mechanisms are unclear. Here, we found that condensin II interacts with a short linear motif in the disordered N-terminal tail of the Bloom syndrome helicase BLM, contributing to BLM association with nascent DNA and genome stability. Disrupting the BLM-condensin II interaction reduced replication speed, increased fork stalling and sister-chromatid exchanges, delayed repair of DNA double-strand breaks, and led to micronuclei. In S phase, interactions of SMC2 with other condensin II subunits and with BLM weakened temporarily, suggesting a conformational change followed by phosphorylation-induced disruption of BLM interactions with TOP2A and RPA. Our findings suggest a new way by which BLM contributes to genome integrity and implicates condensin II in interphase functions linked to genome stability.
脊椎动物拥有两种凝缩蛋白，即凝缩蛋白I和凝缩蛋白II，它们对于染色体凝聚和分离至关重要。凝缩蛋白II也被认为在有丝分裂之外维持基因组完整性方面发挥作用，但其潜在机制尚不清楚。在此，我们发现凝缩蛋白II与布鲁姆综合征解旋酶BLM无序的N端尾巴中的一个短线性基序相互作用，有助于BLM与新生DNA的结合以及基因组稳定性。破坏BLM-凝缩蛋白II的相互作用会降低复制速度，增加叉停滞和姐妹染色单体交换，延迟DNA双链断裂的修复，并导致微核形成。在S期，SMC2与其他凝缩蛋白II亚基以及与BLM的相互作用会暂时减弱，这表明随后会发生构象变化，接着是磷酸化诱导的BLM与TOP2A和RPA相互作用的破坏。我们的研究结果揭示了BLM促进基因组完整性的一种新方式，并表明凝缩蛋白II参与了与基因组稳定性相关的间期功能。
