Component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes (CRLs), which mediate the ubiquitination of target proteins. The CRL associates with CDC34 as the E2 ubiquitin-conjugating enzyme. The functional specificity of the CRL depends on the type of the associated substrate receptor protein. RTT101(MMS1-MMS22) promotes fork progression through damaged DNA or natural pause sites by stabilizing replication proteins like the replication fork-pausing complex (FPC) and leading-strand polymerase at stalled replication forks. RTT101(MMS1-MMS22) ubiquitinates the acetylated histones H3K56ac-H4 at lysine residues H3K121, H3K122 and H3K125. Ubiquitination is required for efficient histone deposition during replication-coupled nucleosome assembly, probably by facilitating the transfer of H3-H4 from ASF1 to other chaperones involved in histone deposition. RTT101(MMS1-CRT10) may regulate nucleotide synthesis through transcriptional regulation of ribonucleotide reductase. RTT101(MMS1) is also involved in the non-functional rRNA decay (NRD) of 25S rRNA through the selective, ubiquitination-dependent degradation of nonfunctional ribosomal particles. Involved in the regulation of TY1 transposition. Component of multiple cullin-RING ligases (CRLs) composed of 4 subunits: the RING protein HRT1, the cullin RTT101, a linker protein MMS1, and one of many alternative substrate receptors belonging to a protein family described as DCAF (DDB1- and CUL4-associated factor). Component of a RTT101(MMS1-MMS22) complex with the substrate receptor MMS22. This complex further interacts with RTT107 and CTF4 to form RTT101-MMS1-MMS22-RTT107 and RTT101-MMS1-MMS22-CTF4 complexes respectively. Component of a RTT101(MSS1-CRT10) complex with the substrate receptor CRT10. Component of a RTT101(MSS1-ESC2) complex with the potential substrate receptor ESC2. Component of a RTT101(MSS1-ORC5) complex with the potential substrate receptor ORC5. Interacts with RTT101 (via N-ter). Interacts (via N-ter) with MMS22 (via C-ter). Interacts with CRT10. Enriched on chromatin at sites where replication forks have stalled.