Zhang, X.; Fawwal, D.V.; Spangle, J.M.; Corbett, A.H.; Jones, C.Y. Exploring the Molecular Underpinnings of Cancer-Causing Oncohistone Mutants Using Yeast as a Model. J. Fungi2023, 9, 1187.
Zhang, X.; Fawwal, D.V.; Spangle, J.M.; Corbett, A.H.; Jones, C.Y. Exploring the Molecular Underpinnings of Cancer-Causing Oncohistone Mutants Using Yeast as a Model. J. Fungi 2023, 9, 1187.
Zhang, X.; Fawwal, D.V.; Spangle, J.M.; Corbett, A.H.; Jones, C.Y. Exploring the Molecular Underpinnings of Cancer-Causing Oncohistone Mutants Using Yeast as a Model. J. Fungi2023, 9, 1187.
Zhang, X.; Fawwal, D.V.; Spangle, J.M.; Corbett, A.H.; Jones, C.Y. Exploring the Molecular Underpinnings of Cancer-Causing Oncohistone Mutants Using Yeast as a Model. J. Fungi 2023, 9, 1187.
Abstract
Understanding the molecular basis of cancer initiation and progression is critical to develop effective treatment strategies. Recently, mutations in genes encoding histone proteins have been identified that drive oncogenesis, converting these essential proteins into “oncohistones”. Understanding how oncohistone mutations, which are commonly missense mutations, subvert the normal function of histones to drive oncogenesis requires defining the functional consequences of such changes. Histones genes are present in multiple copies in the human genome with 15 genes encoding histone H3 isoforms, the histone for which the majority of oncohistone variants have been analyzed thus far. With so many histone genes, engineering human cell lines that assess changes induced by sole expression of the oncohistone variant is technically challenging. In contrast to humans, budding and fission yeast contain only two or three histone H3 genes, respectively. Furthermore, yeast histones share ~90% sequence identity with human H3 protein. The genetic simplicity and evolutionary conservation make yeast an excellent model for characterizing oncohistones. The power of genetic approaches can also be exploited in yeast models to define cellular signaling pathways that could serve as actionable therapeutic targets. In this review, we focus on the value of yeast models to serve as a discovery tool that can inform subsequent translational studies in humans.
Keywords
Histone, Oncohistone, Budding yeast, Fission yeast, Epigenetics, Cancer
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
