Chapter title |
A Regulatory Role for RUNX1, RUNX3 in the Maintenance of Genomic Integrity
|
---|---|
Chapter number | 29 |
Book title |
RUNX Proteins in Development and Cancer
|
Published in |
Advances in experimental medicine and biology, March 2017
|
DOI | 10.1007/978-981-10-3233-2_29 |
Pubmed ID | |
Book ISBNs |
978-9-81-103231-8, 978-9-81-103233-2
|
Authors |
Vaidehi Krishnan, Yoshiaki Ito |
Editors |
Yoram Groner, Yoshiaki Ito, Paul Liu, James C. Neil, Nancy A. Speck, Andre van Wijnen |
Abstract |
All human cells are constantly attacked by endogenous and exogenous agents that damage the integrity of their genomes. Yet, the ensuing damage is mostly fixed and very rarely gives rise to genomic defects that promote cancer formation. This is due to the co-ordinated functioning of DNA repair proteins and checkpoint mechanisms that accurately detect and repair DNA damage to ensure genomic fitness. According to accumulating evidence, the RUNX family of transcription factors participate in the maintenance of genomic stability through transcriptional and non-transcriptional mechanisms. RUNX1 and RUNX3 maintain genomic integrity in a transcriptional manner by regulating the transactivation of apoptotic genes following DNA damage via complex formation with p53. RUNX1 and RUNX3 also maintain genomic integrity in a non-transcriptional manner during interstand crosslink repair by promoting the recruitment of FANCD2 to sites of DNA damage. Since RUNX genes are frequently aberrant in human cancer, here, we argue that one of the major modes by which RUNX inactivation promotes neoplastic transformation is through the loss of genomic integrity. In particular, there exists strong evidence that leukemic RUNX1-fusions such as RUNX1-ETO disrupt genomic integrity and induce a "mutator" phenotype during the early stages of leukemogenesis. Consistent with increased DNA damage accumulation induced by RUNX1-ETO, PARP inhibition has been shown to be an effective synthetic-lethal therapeutic approach against RUNX1-ETO expressing leukemias. Here, in this chapter we will examine current evidence suggesting that the tumor suppressor potential of RUNX proteins can be at least partly attributed to their ability to ensure high-fidelity DNA repair and thus prevent mutational accumulation during cancer progression. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 9 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Other | 1 | 11% |
Student > Bachelor | 1 | 11% |
Student > Ph. D. Student | 1 | 11% |
Student > Master | 1 | 11% |
Researcher | 1 | 11% |
Other | 0 | 0% |
Unknown | 4 | 44% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 2 | 22% |
Nursing and Health Professions | 1 | 11% |
Agricultural and Biological Sciences | 1 | 11% |
Medicine and Dentistry | 1 | 11% |
Unknown | 4 | 44% |