Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway. HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse. Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ). Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA. Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage (By similarity). During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (By similarity). Homodimer; dimerizes via the coiled coil domain. Interacts (via the PXDLS motif) with CTBP1; the interaction is disrupted via binding of the adenovirus E1A to CTBP1. Component of the BRCA1-RBBP8 complex. Interacts (the Ser-321 phosphorylated form) with BRCA1 (via the C-terminal BRCA1 domains): the interaction occurs in the G2 phase, ubiquitinates RBBP8 and involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA damage. Interacts with RB1. Interacts with the MRN complex. Interacts directly with MRE11; the interaction is required for efficient homologous recombination (HR) and regulation of the MRN complex. Interacts directly with RAD50. Interacts directly with NBN. Interacts with LM04 (via the LIM zinc-binding 1 domain). Interacts with SIAH1. Interacts with RNF138. Interacts with EXD2. Interacts with CUL3 and KLHL15; this interaction leads to RBBP8 proteasomal degradation. Directly interacts with PIN1; this interaction depends upon RBBP8 phosphorylation, predominantly at Thr-309. Interacts with FZR1; this interaction leads to APC/C-mediated RBBP8 proteasomal degradation. Interacts with AUNIP; leading to recruit RBBP8 to sites of DNA damage. Interacts with SAMHD1 (By similarity). Interacts with HDGFL2 (By similarity). Associates with sites of DNA damage in S/G2 phase. Ubiquitinated RBBP8 binds to chromatin following DNA damage. The damage-recruitment motif is required for DNA binding and translocation to sites of DNA damage. The PXDLS motif binds to a cleft in CtBP proteins. Hyperphosphorylation upon ionizing radiation results in dissociation from BRCA1. Phosphorylation by CDK1 is essential for the recruitment to DNA and the DNA repair function. Phosphorylated on Ser-321 as cells enter G2 phase. This phosphorylation is required for binding BRCA1 and for the G2/M DNA damage transition checkpoint control (By similarity). Phosphorylation at Thr-309, probably catalyzed by CDK2, is required for PIN1-binding, while phosphorylation at Ser-272 serves as a PIN1 isomerization site. Phosphorylation at Thr-309 is cell-cycle dependent. It steadily increases during S phase, peaks at late S/G2 phase, and drops at G1 (By similarity). Ubiquitinated. Ubiquitination at multiple sites by BRCA1 (via its N-terminal RING domain) does not lead to its proteosomal degradation but instead the ubiquitinated RBBP8 binds to chromatin following DNA damage and may play a role in G2/M checkpoint control. Ubiquitinated by RNF138 at its N-terminus. Ubiquitinated through 'Lys-48' by the E3 CUL3-KLHL15 complex; this modification leads to proteasomal degradation (By similarity). Ubiquitinated by the E3 FZR1/APC/C complex; this modification leads to proteasomal degradation (By similarity). Belongs to the COM1/SAE2/CtIP family.