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Tuesday, 5th, July 2022
Centre de recherche - Paris - Amphith√©√Ętre Marie Curie

Understanding the molecular mechanism of chromosome protection

Faithful chromosome segregation following complete DNA replication is crucial to preserve genome integrity. To achieve equal chromosome segregation, cells need to align condensed chromosomes to the metaphase plate (a process of so-called chromosome biorientation). This requires physical attachment of spindle microtubules (MTs) to the centromeres of sister chromatids through kinetochores (KTs). It is well established that Polo-like kinase 1 (PLK1) plays an essential role during chromosome biorientation by stabilising bipolar MT-KT attachments. Unexpectedly, we find that PLK1 also plays a key function to protect centromere rigidity to withstand bipolar spindle pulling forces. Disabling PLK1 during mitosis causes a hitherto undescribed centromere rupture, named ‘centromere disintegration’. Our further investigation shows that this devastating damage is caused by illegitimate targeting by the ultrafine DNA bridge (UFB)-binding complex, which is composed of PICH DNA translocase, Bloom’s syndrome (BLM) DNA helicase and topoisomerase 3A. The prematurely activated UFB-binding complex initiates acute DNA unwinding at a specific region of the centromeres, promptly dechromatinising the entire centromeres under the assistance of spindle pulling. In this talk, I will discuss how centromeres undergo dechromatinisation, and how PLK1 and other mitotic kinases tightly regulate the UFB-binding complex activity until anaphase onset to protect centromeres. In addition, I will also present our recent findings of how human cells change DNA replication dynamics to lessen mitotic chromatin damage under the challenge of replication stress. 


Dr at the Centre for Genome Damage and Stability, University of Sussex (UK)

Hosted by

Mrs. Annapaola Angrisani

Invited by

Dr. Daniele Fachinetti
Group Leader


Mrs. Annapaola Angrisani

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