AI Article Synopsis
- Mcm10 is a vital protein in eukaryotic DNA replication that helps coordinate essential proteins for synthesizing the lagging strand, especially through its interaction with PCNA.
- Ubiquitination is crucial for Mcm10's function, with lysine 372 identified as the main site for this modification, along with five other potential sites.
- Mutating lysine 372 impairs ubiquitination and increases sensitivity to replication stress, highlighting the importance of this modification in maintaining DNA replication integrity.
Article Abstract
Minichromosome maintenance protein (Mcm) 10 is a part of the eukaryotic replication machinery and highly conserved throughout evolution. As a multivalent DNA scaffold, Mcm10 coordinates the action of proteins that are indispensable for lagging strand synthesis, such as the replication clamp, proliferating cell nuclear antigen (PCNA). The binding between Mcm10 and PCNA serves an essential function during DNA elongation and is mediated by the ubiquitination of Mcm10. Here we map lysine 372 as the primary attachment site for ubiquitin on Mcm10. Moreover, we identify five additional lysines that can be ubiquitinated. Mutation of lysine 372 to arginine ablates ubiquitination of overexpressed protein and causes sensitivity to the replication inhibitor hydroxyurea in cells that are S-phase checkpoint compromised. Together, these findings reveal the high selectivity of the ubiquitination machinery that targets Mcm10 and that ubiquitination has a role in suppressing replication stress.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421568 | PMC |
| http://dx.doi.org/10.1016/j.bbrep.2016.09.003 | DOI Listing |
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