The RBBP6/ZBTB38/MCM10 Axis Regulates DNA Replication and Common Fragile Site Stability

• DOI: 10.1016/j.celrep.2014.03.030
• Publication Date: 2014-04-13T19:15:13Z
• Authors: Benoit Miotto; Moredreck Chibi; Ping Xie; Stéphane Koundrio...; Hanlie Moolman-Smook; David Pugh; Michelle Debatisse; Fuchu He; Lingqiang Zhang; Pierre-Antoine De...
• Keywords: Origin recognition complex; Replication factor C; Pre-replication complex; Chromosomal fragile site; SeqA protein domain

Faithful DNA replication is essential for the maintenance of genome integrity.Incomplete leads to breaks and chromosomal rearrangements, which are causal factors in cancer other human diseases.Despite their importance, molecular mechanisms that control stability incompletely understood.Here, we report a pathway required stability.This has three components: an E3 ubiquitin ligase, transcriptional repressor, protein.The ligase RBBP6 ubiquitinates destabilizes repressor ZBTB38.This negatively regulates transcription levels MCM10 factor on chromatin.Cells lacking experience reduced fork progression increased damage at common fragile sites due ZBTB38 accumulation downregulation.Our results uncover ensures genome-wide stability.