Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis.

Journal article

Translesion synthesis (TLS) is the major pathway by which mammalian cells replicate across DNA lesions. Upon DNA damage, ubiquitination of proliferating cell nuclear antigen (PCNA) induces bypass of the lesion by directing the replication machinery into the TLS pathway. Yet, how this modification is recognized and interpreted in the cell remains unclear. Here we describe the identification of two ubiquitin (Ub)-binding domains (UBM and UBZ), which are evolutionarily conserved in all Y-family TLS polymerases (pols). These domains are required for binding of poleta and poliota to ubiquitin, their accumulation in replication factories, and their interaction with monoubiquitinated PCNA. Moreover, the UBZ domain of poleta is essential to efficiently restore a normal response to ultraviolet irradiation in xeroderma pigmentosum variant (XP-V) fibroblasts. Our results indicate that Ub-binding domains of Y-family polymerases play crucial regulatory roles in TLS.

Authors: Bienko, M; Green, C; Crosetto, N; Rudolf, F; Zapart, G

• Publication status: Published
• Journal: Science (New York, N.Y.)
• Volume: 310
• Issue: 5755
• Pages: 1821-1824
• Publication date: 2005-12-01
• DOI: 10.1126/science.1120615
• EISSN: 1095-9203
• ISSN: 0036-8075
• Language: English
• Keywords: DNA Replication; Animals; Ubiquitin; Proliferating Cell Nuclear Antigen; DNA-Directed DNA Polymerase; Protein Binding; Computational Biology; Protein Structure, Tertiary; Nuclear Magnetic Resonance, Biomolecular; Models, Molecular; Protein Interaction Mapping; Mutation; Humans; Hydrophobic and Hydrophilic Interactions; Amino Acid Motifs; DNA; Point Mutation; Molecular Sequence Data; Protein Conformation; Cell Line; DNA Repair; DNA Damage; Amino Acid Sequence; Recombinant Fusion Proteins; Zinc Fingers; Xeroderma Pigmentosum; Transfection