LC8 enhances 53BP1 foci through heterogeneous bridging of 53BP1 oligomers.

ABSTRACT: 53BP1 is a key player in DNA repair and together with BRCA1 regulate selection of DNA double-strand break repair mechanisms. Localization of DNA repair factors to sites of DNA damage by 53BP1 is controlled by its oligomerization domain (OD) and binding to LC8, a hub protein that functions to dimerize >100 clients. Here, we show that 53BP1 OD is a trimer, an unusual finding for LC8 clients which are all dimers or tetramers. As a trimer, 53BP1 forms a heterogeneous mixture of complexes when bound to dimeric LC8, with the largest mass corresponding to a dimer-of-trimers bridged by 3 LC8 dimers. Analytical ultracentrifugation and isothermal titration calorimetry demonstrate that only the second of the three LC8 recognition motifs is necessary for a stable bridged complex. The stability of the

SUBMITTER: Howe J 

PROVIDER: S-EPMC12187134 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature