Research Focus Area:
Diagnosis/ Prognosis, Carcinogenesis
Type of Research:
Research Interest Statement:
The following is the Relevance Statement from my R35 grant: A major focus of the project is DNA replication, a fundamental event that is required in all life forms, and its disruption can lead to several forms of disease, including cancer. The central engine of the replication machinery is the hexameric MCM complex that unwinds DNA at the replication fork once the tightly regulated replication process begins. MCMs and the kinases that activate them are logical, promising targets for anti-cancer therapies. A second focus of the project is the human RNA helicase DDX3X, which is associated with several human diseases, including HIV, HCV, and the brain cancer medulloblastoma. Mutation of this gene has been linked to medulloblastoma by genetic sequencing studies.
“Molecular mechanisms of nucleic acid machines-Continuation”
11/24/20 – 05/31/25
NIGMS – 7R01GM098771
“Molecular mechanisms of DNA replication”
11/24/20 – 08/31/22
Meagher M, Spence MN, Enemark EJ. Structure of a dimer of the Sulfolobus solfataricus MCM N-terminal domain reveals a potential role in MCM ring opening. Acta crystallographica. Section F, Structural biology communications. 2021 77(Pt 6):177-186. PMID: 34100776.
Meagher M, Epling LB, Enemark EJ. DNA translocation mechanism of the MCM complex and implications for replication initiation. Nature communications. 2019 10(1):3117. PMID: 31308367. PMCID: PMC6629641.
Iacobucci I, Wen J, Meggendorfer M, [et al., including Enemark EJ]. Genomic subtyping and therapeutic targeting of acute erythroleukemia. Nature genetics. 2019 51(4):694-704. PMID: 30926971. PMCID: PMC6828160.
Meagher M, Enemark EJ. Structure of a double hexamer of the Pyrococcus furiosus minichromosome maintenance protein N-terminal domain. Acta crystallographica. Section F, Structural biology communications. 2016 72(Pt 7):545-51. PMID: 27380371. PMCID: PMC4933004.
Miller JM, Enemark EJ. Fundamental Characteristics of AAA+ Protein Family Structure and Function. Archaea (Vancouver, B.C.). 2016 2016:9294307. PMID: 27703410. PMCID: PMC5039278.
Froelich CA, Nourse A, Enemark EJ. MCM ring hexamerization is a prerequisite for DNA-binding. Nucleic acids research. 2015 43(19):9553-63. PMID: 26365238. PMCID: PMC4627082.