Publications by authors named "Alicja Reynolds-Winczura"
The eukaryotic replicative helicase (CMG complex) is assembled during DNA replication initiation in a highly regulated manner, which is described in depth by other manuscripts in this Issue. During DNA replication, the replicative helicase moves through the chromatin, unwinding DNA and facilitating nascent DNA synthesis by polymerases. Once the duplication of a replicon is complete, the CMG helicase and the remaining components of the replisome need to be removed from the chromatin.
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- - The MCM motor, initially inactive as a double hexamer, is crucial for DNA replication and becomes activated through the recruitment of proteins GINS and Cdc45 during the S-phase of the cell cycle.
- - Research reveals that the metazoan protein Downstream neighbor of Son (DONSON) plays a key role in the assembly of active CMG helicases by delivering GINS to MCM, though the specific effects on the MCM structure were unclear prior to this study.
- - Using cryoelectron microscopy on Xenopus egg extracts, the study identifies a double CMG complex connected by a DONSON dimer, showing that this tethering is vital for DNA replication, with mutations in DONSON linked to issues in human
Faithful cell division is the basis for the propagation of life and DNA replication must be precisely regulated. DNA replication stress is a prominent endogenous source of genome instability that not only leads to ageing, but also neuropathology and cancer development in humans. Specifically, the issues of how vertebrate cells select and activate origins of replication are of importance as, for example, insufficient origin firing leads to genomic instability and mutations in replication initiation factors lead to the rare human disease Meier-Gorlin syndrome.
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- Cell division depends on accurate DNA replication, and errors during this process can lead to serious health issues like cancer and premature aging.
- TRAIP E3 ubiquitin ligase is crucial for maintaining genome integrity and cell survival, and its dysfunction is linked to conditions like primordial dwarfism.
- Research using the auxin-induced degron system showed that when TRAIP is depleted, cells stop dividing during the S-phase, get stuck in the G2 phase, and eventually enter senescence due to DNA damage during transcription.