“…Indeed, we also know from biology that catalytically inactive proteins that bind and hold damaged DNA can control damage outcomes, as seen for ATL that forms a complex with alkylated base damage and thereby alters repair pathway outcome from base repair to the nucleotide excision repair pathway ( Tubbs et al, 2009 ). Analogously, XPG impacts multiple repair pathways by binding and sculpting DNA junctions and protein partners in addition to its nuclease activity ( Tsutakawa et al, 2020 ), FEN1 sculpts 5’ flaps to avoid template switching at replication forks ( Perry et al, 2006 , Trego et al, 2011 , Tsutakawa et al, 2017 ), GRB2 adaptor protein efficiently brings MRE11 nuclease to DNA breaks ( Ye et al, 2021 ), XRCC1 links MRE11 and PolQ to promote alternative end joining of DNA breaks ( Eckelmann et al, 2020 ), SLX4IP binds and maintains SLX4-XPF-ERCC1 complex for inter-strand crosslink repair ( Zhang et al, 2019 ), and acetylation targets oxidative base repair initiation to open chromatin ( Bacolla et al, 2021 ). In extreme examples, transient polyvalent binding by flexible proteins and RNA can create phase separated condensates of functional proteins for processes such as repair, as seen for DNA break repair protein KU and its complex with long non-coding RNA ( Thapar et al, 2021 ).…”