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Structural basis of HMCES interactions with abasic DNA and multivalent substrate recognition
HMCES can covalently crosslink to abasic sites in single-stranded DNA at stalled replication forks to prevent genome instability. Here, we report crystal structures of the Human HMCES SRAP domain in complex with DNA-damage substrates, including HMCES crosslinked with an abasic site within a 3’ overh...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609482/ https://www.ncbi.nlm.nih.gov/pubmed/31235913 http://dx.doi.org/10.1038/s41594-019-0246-6 |
Sumario: | HMCES can covalently crosslink to abasic sites in single-stranded DNA at stalled replication forks to prevent genome instability. Here, we report crystal structures of the Human HMCES SRAP domain in complex with DNA-damage substrates, including HMCES crosslinked with an abasic site within a 3’ overhang DNA. HMCES interacts with both single-strand and duplex segments of DNA, with two independent duplex DNA interaction sites identified in the SRAP domain. The HMCES DNA-protein crosslink structure provides structural insights into a novel thiazolidine covalent interaction between the DNA abasic site and conserved Cys2 of HMCES. Collectively, our structures demonstrate the capacity for the SRAP domain to interact with variety of single-strand and double-strand containing DNA structures found in DNA-damage sites including 5’ and 3’ overhang DNAs and gapped DNAs with short single-strand segments. |
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