What is it about?
Tumor suppressor TP53 gene is frequently altered mostly by missense mutations in majority of human cancer and thereby lose its tumor suppression function . Moreover, certain p53 mutants known as "gain-of-function mutant p53 "promote tumorigenesis by regulating various signaling pathways inside the cells. In this work, we have investigated how mutant p53 regulates DNA replication in cancer cells. We report that in presence of mutant p53 activity of replication initiation factor Cdc7 kinase is increased that in turn promote replication origin firing or replication initiation. We also report that perturbation of increase replication initiation by depleting Cdc7 kinase is effective in reducing tumor growth in mutant p53 bearing cancer cells. We propose that targeting Cdc7 kinase may be useful in treating aggressive tumors that carry TP53 mutations.
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Why is it important?
This study reveals new area i.e. modulation of DNA replication in the context of mutant p53 "gain-of-function" research.
Perspectives
This publication describes novel molecular interaction between gain-of-function mutant p53 and DNA replication in cancer cells. I consider this article thought-provoking and hope that this article will be helpful to researchers to further unravel the molecular mechanisms of enhanced tumorigenesis conferred by mutant p53.
Arindam Datta
CSIR-Indian Institute of Chemical Biology
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This page is a summary of: p53 gain‐of‐function mutations increase Cdc7‐dependent replication initiation, EMBO Reports, September 2017, EMBO,
DOI: 10.15252/embr.201643347.
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