Structural basis of DNA replication origin recognition by human Orc6 protein binding with DNA
| Autor: | Maxim Balasov, Pei-Yuan Qian, Katarina Akhmetova, Haitao Miao, Changdong Liu, Chun Po Fung, To To Choy, Hongyu Yang, Igor Chesnokov, Guang Zhu, Lee Tung Lun, Rahman Ud Din, Honglei Tian, Naining Xu, Yingying You, Bo Zhou, Yanyan Geng, Quan Hao, Xiao Shi, Zhuming Fan |
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| Rok vydání: | 2020 |
| Předmět: |
DNA Replication
AcademicSubjects/SCI00010 Protein subunit Origin Recognition Complex Replication Origin Biology Origin of replication 03 medical and health sciences ORC6 chemistry.chemical_compound 0302 clinical medicine Protein Domains Structural Biology Genetics Humans 030304 developmental biology 0303 health sciences DNA replication DNA DNA replication origin Cell biology chemistry Origin recognition complex Transcription factor II B 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkaa751 |
| Popis: | The six-subunit origin recognition complex (ORC), a DNA replication initiator, defines the localization of the origins of replication in eukaryotes. The Orc6 subunit is the smallest and the least conserved among ORC subunits. It is required for DNA replication and essential for viability in all species. Orc6 in metazoans carries a structural homology with transcription factor TFIIB and can bind DNA on its own. Here, we report a solution structure of the full-length human Orc6 (HsOrc6) alone and in a complex with DNA. We further showed that human Orc6 is composed of three independent domains: N-terminal, middle and C-terminal (HsOrc6-N, HsOrc6-M and HsOrc6-C). We also identified a distinct DNA-binding domain of human Orc6, named as HsOrc6-DBD. The detailed analysis of the structure revealed novel amino acid clusters important for the interaction with DNA. Alterations of these amino acids abolish DNA-binding ability of Orc6 and result in reduced levels of DNA replication. We propose that Orc6 is a DNA-binding subunit of human/metazoan ORC and may play roles in targeting, positioning and assembling the functional ORC at the origins. |
| Databáze: | OpenAIRE |
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