Work

Faculty Opinions recommendation of DNA-dependent protease activity of human Spartan facilitates replication of DNA-protein crosslink-containing DNA.

Year: 2019

Type: peer-review

Abstract: Mutations in SPARTAN are associated with early onset hepatocellular carcinoma and progeroid features.A regulatory function of Spartan has been implicated in DNA damage tolerance pathways such as translesion synthesis, but the exact function of the protein remained unclear.Here, we reveal the role of human Spartan in facilitating replication of DNA-protein crosslink-containing DNA.We found that purified Spartan has a DNA-dependent protease activity degrading certain proteins bound to DNA.In concert, Spartan is required for direct DPC removal in vivo; we also show that the protease Spartan facilitates repair of formaldehyde-induced DNAprotein crosslinks in later phases of replication using the bromodeoxyuridin (BrdU) comet assay.Moreover, DNA fibre assay indicates that formaldehydeinduced replication stress dramatically decreases the speed of replication fork movement in Spartandeficient cells, which accumulate in the G2/M cell cycle phase.Finally, epistasis analysis mapped these Spartan functions to the RAD6-RAD18 DNA damage tolerance pathway.Our results reveal that Spartan facilitates replication of DNA-protein crosslinkcontaining DNA enzymatically, as a protease, which may explain its role in preventing carcinogenesis and aging.

Source: Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

DOI: 10.3410/f.727169744.793565206

Author: Scott Kaufmann

Institution: Mayo Clinic

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Magyar Tudományos Akadémia, National Research, Development and Innovation Office