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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
The RBBP6/ZBTB38/MCM10 Axis Regulates DNA Replication and Common Fragile Site Stability
Cell Reports, Volume 7, No. 2, Year 2014
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Description
Faithful DNA replication is essential for the maintenance of genome integrity. Incomplete genome replication leads to DNA breaks and chromosomal rearrangements, which are causal factors in cancer and other human diseases. Despite their importance, the molecular mechanisms that control human genome stability are incompletely understood. Here, we report a pathway that is required for human genome replication and stability. This pathway has three components: an E3 ubiquitin ligase, a transcriptional repressor, and a replication protein. The E3 ubiquitin ligase RBBP6 ubiquitinates and destabilizes the transcriptional repressor ZBTB38. This repressor negatively regulates transcription and levels of the MCM10 replication factor on chromatin. Cells lacking RBBP6 experience reduced replication fork progression and increased damage at common fragile sites due to ZBTB38 accumulation and MCM10 downregulation. Our results uncover a pathway that ensures genome-wide DNA replication and chromosomal stability. © 2014 The Authors.
Authors & Co-Authors
Miotto, Benoit
France, Paris
Epigénétique et Destin Cellulaire
Chibi, Moredreck
France, Paris
Epigénétique et Destin Cellulaire
South Africa, Bellville
University of the Western Cape
Xie, Ping
China, Beijing
Beijing Institute of Radiation Medicine
China, Dalian
Dalian Medical University
Koundrioukoff, Stéphane
France, Paris
Cnrs Centre National de la Recherche Scientifique
Moolman-Smook, Hanlie
South Africa, Stellenbosch
Stellenbosch University
Pugh, David J.R.
South Africa, Bellville
University of the Western Cape
Debatisse, Michelle
France, Paris
Cnrs Centre National de la Recherche Scientifique
He, Fuchu
China, Beijing
Beijing Institute of Radiation Medicine
Zhang, Lingqiang
China, Beijing
Beijing Institute of Radiation Medicine
China, Dalian
Dalian Medical University
Defossez, Pierre Antoine
France, Paris
Epigénétique et Destin Cellulaire
Statistics
Citations: 73
Authors: 10
Affiliations: 6
Identifiers
Doi:
10.1016/j.celrep.2014.03.030
e-ISSN:
22111247
Research Areas
Cancer
Genetics And Genomics