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Ubiquitin-Binding Domains in Y-Family Polymerases Regulate Translesion Synthesis
- Source :
- Science. 310:1821-1824
- Publication Year :
- 2005
- Publisher :
- American Association for the Advancement of Science (AAAS), 2005.
-
Abstract
- 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 polη and polι to ubiquitin, their accumulation in replication factories, and their interaction with monoubiquitinated PCNA. Moreover, the UBZ domain of polη 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.
- Subjects :
- DNA Replication
Models, Molecular
Xeroderma pigmentosum
DNA Repair
Ubiquitin binding
Protein Conformation
DNA repair
Recombinant Fusion Proteins
Amino Acid Motifs
Molecular Sequence Data
DNA-Directed DNA Polymerase
DNA polymerase eta
Transfection
Cell Line
Ubiquitin
Proliferating Cell Nuclear Antigen
Protein Interaction Mapping
medicine
Animals
Humans
Point Mutation
Amino Acid Sequence
Nuclear Magnetic Resonance, Biomolecular
Xeroderma Pigmentosum
Multidisciplinary
biology
DNA replication
Computational Biology
Zinc Fingers
DNA
medicine.disease
Protein Structure, Tertiary
Proliferating cell nuclear antigen
Biochemistry
Mutation
DNA Polymerase iota
biology.protein
REV1
Hydrophobic and Hydrophilic Interactions
DNA Damage
Protein Binding
Subjects
Details
- ISSN :
- 10959203 and 00368075
- Volume :
- 310
- Database :
- OpenAIRE
- Journal :
- Science
- Accession number :
- edsair.doi.dedup.....2363c71f50a597c94225447790a6fdb2
- Full Text :
- https://doi.org/10.1126/science.1120615