Biochemistry: Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2005
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| _version_ | 1826290730299031552 |
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| author | Bienko, M Green, C Crosetto, N Rudolf, F Zapart, G Coull, B Kannouche, P Wider, G Peter, M Lehmann, A Hofmann, K Dikic, I |
| author_facet | Bienko, M Green, C Crosetto, N Rudolf, F Zapart, G Coull, B Kannouche, P Wider, G Peter, M Lehmann, A Hofmann, K Dikic, I |
| author_sort | Bienko, M |
| collection | OXFORD |
| description | 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 poll 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. |
| first_indexed | 2024-03-07T02:48:40Z |
| format | Journal article |
| id | oxford-uuid:ace9a1d7-cb87-49b7-aa8b-4a05d2585fc6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:48:40Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:ace9a1d7-cb87-49b7-aa8b-4a05d2585fc62022-03-27T03:32:03ZBiochemistry: Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ace9a1d7-cb87-49b7-aa8b-4a05d2585fc6EnglishSymplectic Elements at Oxford2005Bienko, MGreen, CCrosetto, NRudolf, FZapart, GCoull, BKannouche, PWider, GPeter, MLehmann, AHofmann, KDikic, ITranslesion 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 poll 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. |
| spellingShingle | Bienko, M Green, C Crosetto, N Rudolf, F Zapart, G Coull, B Kannouche, P Wider, G Peter, M Lehmann, A Hofmann, K Dikic, I Biochemistry: Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis |
| title | Biochemistry: Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis |
| title_full | Biochemistry: Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis |
| title_fullStr | Biochemistry: Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis |
| title_full_unstemmed | Biochemistry: Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis |
| title_short | Biochemistry: Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis |
| title_sort | biochemistry ubiquitin binding domains in y family polymerases regulate translesion synthesis |
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