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A fragmented alignment method detects a putative phosphorylation site and a putative BRC repeat in the Drosophila melanogaster BRCA2 protein
Mutations in the BRCA2 tumor suppressor protein leave individuals susceptible to breast, ovarian and other cancers. The BRCA2 protein is a critical component of the DNA repair pathways in eukaryotes, and also plays an integral role in fostering genomic variability through meiotic recombination. Alth...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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F1000Research
2013
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924952/ https://www.ncbi.nlm.nih.gov/pubmed/24627786 http://dx.doi.org/10.12688/f1000research.2-143.v2 |
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author | Chakraborty, Sandeep |
author_facet | Chakraborty, Sandeep |
author_sort | Chakraborty, Sandeep |
collection | PubMed |
description | Mutations in the BRCA2 tumor suppressor protein leave individuals susceptible to breast, ovarian and other cancers. The BRCA2 protein is a critical component of the DNA repair pathways in eukaryotes, and also plays an integral role in fostering genomic variability through meiotic recombination. Although present in many eukaryotes, as a whole the BRCA2 gene is weakly conserved. Conserved fragments of 30 amino acids (BRC repeats), which mediate interactions with the recombinase RAD51, helped detect orthologs of this protein in other organisms. The carboxy-terminal of the human BRCA2 has been shown to be phosphorylated by checkpoint kinases (Chk1/Chk2) at T3387, which regulate the sequestration of RAD51 on DNA damage. However, apart from three BRC repeats, the Drosophila melanogaster gene has not been annotated and associated with other functionally relevant sequence fragments in human BRCA2. In the current work, the carboxy-terminal phosphorylation threonine site (E=9.1e-4) and a new BRC repeat (E=17e-4) in D. melanogaster has been identified, using a fragmented alignment methodology (FRAGAL). In a similar study, FRAGAL has also identified a novel half-a- tetratricopeptide (HAT) motif (E=11e-4), a helical repeat motif implicated in various aspects of RNA metabolism, in Utp6 from yeast. The characteristic three aromatic residues with conserved spacing are observed in this new HAT repeat, further strengthening my claim. The reference and target sequences are sliced into overlapping fragments of equal parameterized lengths. All pairs of fragments in the reference and target proteins are aligned, and the gap penalties are adjusted to discourage gaps in the middle of the alignment. The results of the best matches are sorted based on differing criteria to aid the detection of known and putative sequences. The source code for FRAGAL results on these sequences is available at https://github.com/sanchak/FragalCode, while the database can be accessed at www.sanchak.com/fragal.htm l. |
format | Online Article Text |
id | pubmed-3924952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | F1000Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-39249522014-03-12 A fragmented alignment method detects a putative phosphorylation site and a putative BRC repeat in the Drosophila melanogaster BRCA2 protein Chakraborty, Sandeep F1000Res Research Article Mutations in the BRCA2 tumor suppressor protein leave individuals susceptible to breast, ovarian and other cancers. The BRCA2 protein is a critical component of the DNA repair pathways in eukaryotes, and also plays an integral role in fostering genomic variability through meiotic recombination. Although present in many eukaryotes, as a whole the BRCA2 gene is weakly conserved. Conserved fragments of 30 amino acids (BRC repeats), which mediate interactions with the recombinase RAD51, helped detect orthologs of this protein in other organisms. The carboxy-terminal of the human BRCA2 has been shown to be phosphorylated by checkpoint kinases (Chk1/Chk2) at T3387, which regulate the sequestration of RAD51 on DNA damage. However, apart from three BRC repeats, the Drosophila melanogaster gene has not been annotated and associated with other functionally relevant sequence fragments in human BRCA2. In the current work, the carboxy-terminal phosphorylation threonine site (E=9.1e-4) and a new BRC repeat (E=17e-4) in D. melanogaster has been identified, using a fragmented alignment methodology (FRAGAL). In a similar study, FRAGAL has also identified a novel half-a- tetratricopeptide (HAT) motif (E=11e-4), a helical repeat motif implicated in various aspects of RNA metabolism, in Utp6 from yeast. The characteristic three aromatic residues with conserved spacing are observed in this new HAT repeat, further strengthening my claim. The reference and target sequences are sliced into overlapping fragments of equal parameterized lengths. All pairs of fragments in the reference and target proteins are aligned, and the gap penalties are adjusted to discourage gaps in the middle of the alignment. The results of the best matches are sorted based on differing criteria to aid the detection of known and putative sequences. The source code for FRAGAL results on these sequences is available at https://github.com/sanchak/FragalCode, while the database can be accessed at www.sanchak.com/fragal.htm l. F1000Research 2013-10-07 /pmc/articles/PMC3924952/ /pubmed/24627786 http://dx.doi.org/10.12688/f1000research.2-143.v2 Text en Copyright: © 2013 Chakraborty S http://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/publicdomain/zero/1.0/ Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication). |
spellingShingle | Research Article Chakraborty, Sandeep A fragmented alignment method detects a putative phosphorylation site and a putative BRC repeat in the Drosophila melanogaster BRCA2 protein |
title | A fragmented alignment method detects a putative phosphorylation site and a putative BRC repeat in the
Drosophila melanogaster BRCA2 protein |
title_full | A fragmented alignment method detects a putative phosphorylation site and a putative BRC repeat in the
Drosophila melanogaster BRCA2 protein |
title_fullStr | A fragmented alignment method detects a putative phosphorylation site and a putative BRC repeat in the
Drosophila melanogaster BRCA2 protein |
title_full_unstemmed | A fragmented alignment method detects a putative phosphorylation site and a putative BRC repeat in the
Drosophila melanogaster BRCA2 protein |
title_short | A fragmented alignment method detects a putative phosphorylation site and a putative BRC repeat in the
Drosophila melanogaster BRCA2 protein |
title_sort | fragmented alignment method detects a putative phosphorylation site and a putative brc repeat in the
drosophila melanogaster brca2 protein |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924952/ https://www.ncbi.nlm.nih.gov/pubmed/24627786 http://dx.doi.org/10.12688/f1000research.2-143.v2 |
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