The role of the MORF/MRG family of genes in cell growth, differentiation, DNA repair, and thereby aging.
The discovery that replicative cellular senescence is a dominant phenotype over immortality led to the discovery that there are at least four unique genetic subgroups of immortal cell lines that use distinct mechanistic pathways to evade cell cycle exit. Study of one of these genetic complementation groups demonstrated that one gene, MORF4, possessed the ability to induce senescence in group B cell lines. The MRG family of genes, of which MORF4 is a member, has since proven important for cellular aging, proliferation, positive and negative transcriptional regulation, and DNA damage repair. MRG15, the evolutionary ancestor of the family, is highly conserved in yeast, C. elegans, drosophila, plants, and mammals and has been implicated in chromatin remodeling in these species. Our proteomics studies have found that MRG15 is unique among mammalian genes in that it associates with both histone deacetylases and histone acetyl transferase complexes, and thus potentially plays a role in both transcriptional silencing and activation. Its knockout in mice is embryonic lethal, resulting in improper organogenesis, as well as cell proliferation and DNA damage repair defects. Future study of these genes will help clarify the role of chromatin remodeling in aging, cellular proliferation, and DNA damage repair.
Pena
Andreana N
AN
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, STCBM Building, 15355 Lambda Drive, San Antonio, TX 78245-3207, USA. penaa2@uthscsa.edu
Pereira-Smith
Olivia M
OM
D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D000071438:Fatty Acid-Binding Protein 7; D051548:Histone Acetyltransferases / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*
D002352:Carrier Proteins; D002843:Chromatin; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; C470833:MORF4L1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051548:Histone Acetyltransferases; C487137:KAT6B protein, human