biostudies-literatureJia JDeutsche ForschungsgemeinschaftAlexander von Humboldt-StiftungChinese Scholarship Council - PhD fellowship to J.J.Georg-August-Universität GöttingenFreie Universität Berlin5535https://www.ebi.ac.uk/biostudies/studies/S-EPMC7608686biostudies-literatureUnknown11(1)The ASCC3 subunit of the activating signal co-integrator complex is a dual-cassette Ski2-like nucleic acid helicase that provides single-stranded DNA for alkylation damage repair by the α-ketoglutarate-dependent dioxygenase AlkBH3. Other ASCC components integrate ASCC3/AlkBH3 into a complex DNA repair pathway. We mapped and structurally analyzed interacting ASCC2 and ASCC3 regions. The ASCC3 fragment comprises a central helical domain and terminal, extended arms that clasp the compact ASCC2 unit. ASCC2-ASCC3 interfaces are evolutionarily highly conserved and comprise a large number of residues affected by somatic cancer mutations. We quantified contributions of protein regions to the ASCC2-ASCC3 interaction, observing that changes found in cancers lead to reduced ASCC2-ASCC3 affinity. FuncNature communicationsThe interaction of DNA repair factors ASCC2 and ASCC3 is affected by somatic cancer mutations.PMC7608686BO3442/1-2SFB860FUB-QBIPostdoctoral fellowship to A.J.P.B.n.a.Bohnsack KEHackert PAbsmeier EHolton NWahl MCPietrzyk-Brzezinska AJBohnsack MTJia JfalseThe interaction of DNA repair factors ASCC2 and ASCC3 is affected by somatic cancer mutations.The ASCC3 subunit of the activating signal co-integrator complex is a dual-cassette Ski2-like nucleic acid helicase that provides single-stranded DNA for alkylation damage repair by the α-ketoglutarate-dependent dioxygenase AlkBH3. Other ASCC components integrate ASCC3/AlkBH3 into a complex DNA repair pathway. We mapped and structurally analyzed interacting ASCC2 and ASCC3 regions. The ASCC3 fragment comprises a central helical domain and terminal, extended arms that clasp the compact ASCC2 unit. ASCC2-ASCC3 interfaces are evolutionarily highly conserved and comprise a large number of residues affected by somatic cancer mutations. We quantified contributions of protein regions to the ASCC2-ASCC3 interaction, observing that changes found in cancers lead to reduced ASCC2-ASCC3 affinity. Func2020-01-01T00:00:00Z2020 Nov2026-05-02T22:48:13.845Z2020-11-19T16:59:52ZS-EPMC76086863313969710.1038/s41467-020-19221-x