Role of a BRCT domain in the interaction of DNA ligase III-alpha with the DNA repair protein XRCC1.
The BRCT domain (for BRCA1 carboxyl terminus) is a protein motif of unknown function, comprising approximately 100 amino acids in five conserved blocks denoted A-E. BRCT domains are present in the tumour suppressor protein BRCA1 [1-3], and the domain is found in over 40 other proteins, defining a su...
| Main Authors: | , , , |
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| Format: | Journal article |
| Sprog: | English |
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1998
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| _version_ | 1826277143080861696 |
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| author | Taylor, R Wickstead, B Cronin, S Caldecott, K |
| author_facet | Taylor, R Wickstead, B Cronin, S Caldecott, K |
| author_sort | Taylor, R |
| collection | OXFORD |
| description | The BRCT domain (for BRCA1 carboxyl terminus) is a protein motif of unknown function, comprising approximately 100 amino acids in five conserved blocks denoted A-E. BRCT domains are present in the tumour suppressor protein BRCA1 [1-3], and the domain is found in over 40 other proteins, defining a superfamily that includes DNA ligase III-alpha and the essential human DNA repair protein XRCC1. DNA ligase III-alpha and XRCC1 interact via their carboxyl termini, close to or within regions that contain a BRCT domain [4]. To examine whether the primary role of the carboxy-terminal BRCT domain of XRCC1 (denoted BRCT II) is to mediate the interaction with DNA ligase III-alpha, we identified the regions of the domain that are required and sufficient for the interaction. An XRCC1 protein in which the conserved D-block tryptophan was disrupted by point mutation retained the ability to interact with DNA ligase III-alpha, so this tryptophan must mediate a different, although conserved, role. XRCC1 in which the weakly conserved C-block was mutated lost the ability to interact with DNA ligase III-alpha. Moreover, 20 amino acids spanning the C-block of BRCT II conferred full DNA ligase III-alpha binding activity upon an unrelated polypeptide. An XRCC1 protein in which this 20mer was deleted could not maintain normal levels of DNA ligase III-alpha in transfected rodent cells, a phenotype associated with defective repair [5]. In summary, these data demonstrate that a BRCT domain can mediate a biologically important protein-protein interaction, and support the existence of additional roles. |
| first_indexed | 2024-03-06T23:24:27Z |
| format | Journal article |
| id | oxford-uuid:69e363fc-9ec9-4c8d-9b2c-51b0a2e00f87 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:24:27Z |
| publishDate | 1998 |
| record_format | dspace |
| spelling | oxford-uuid:69e363fc-9ec9-4c8d-9b2c-51b0a2e00f872022-03-26T18:53:54ZRole of a BRCT domain in the interaction of DNA ligase III-alpha with the DNA repair protein XRCC1.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:69e363fc-9ec9-4c8d-9b2c-51b0a2e00f87EnglishSymplectic Elements at Oxford1998Taylor, RWickstead, BCronin, SCaldecott, KThe BRCT domain (for BRCA1 carboxyl terminus) is a protein motif of unknown function, comprising approximately 100 amino acids in five conserved blocks denoted A-E. BRCT domains are present in the tumour suppressor protein BRCA1 [1-3], and the domain is found in over 40 other proteins, defining a superfamily that includes DNA ligase III-alpha and the essential human DNA repair protein XRCC1. DNA ligase III-alpha and XRCC1 interact via their carboxyl termini, close to or within regions that contain a BRCT domain [4]. To examine whether the primary role of the carboxy-terminal BRCT domain of XRCC1 (denoted BRCT II) is to mediate the interaction with DNA ligase III-alpha, we identified the regions of the domain that are required and sufficient for the interaction. An XRCC1 protein in which the conserved D-block tryptophan was disrupted by point mutation retained the ability to interact with DNA ligase III-alpha, so this tryptophan must mediate a different, although conserved, role. XRCC1 in which the weakly conserved C-block was mutated lost the ability to interact with DNA ligase III-alpha. Moreover, 20 amino acids spanning the C-block of BRCT II conferred full DNA ligase III-alpha binding activity upon an unrelated polypeptide. An XRCC1 protein in which this 20mer was deleted could not maintain normal levels of DNA ligase III-alpha in transfected rodent cells, a phenotype associated with defective repair [5]. In summary, these data demonstrate that a BRCT domain can mediate a biologically important protein-protein interaction, and support the existence of additional roles. |
| spellingShingle | Taylor, R Wickstead, B Cronin, S Caldecott, K Role of a BRCT domain in the interaction of DNA ligase III-alpha with the DNA repair protein XRCC1. |
| title | Role of a BRCT domain in the interaction of DNA ligase III-alpha with the DNA repair protein XRCC1. |
| title_full | Role of a BRCT domain in the interaction of DNA ligase III-alpha with the DNA repair protein XRCC1. |
| title_fullStr | Role of a BRCT domain in the interaction of DNA ligase III-alpha with the DNA repair protein XRCC1. |
| title_full_unstemmed | Role of a BRCT domain in the interaction of DNA ligase III-alpha with the DNA repair protein XRCC1. |
| title_short | Role of a BRCT domain in the interaction of DNA ligase III-alpha with the DNA repair protein XRCC1. |
| title_sort | role of a brct domain in the interaction of dna ligase iii alpha with the dna repair protein xrcc1 |
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