3eu7: Difference between revisions
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{{STRUCTURE_3eu7| PDB=3eu7 | SCENE= }} | {{STRUCTURE_3eu7| PDB=3eu7 | SCENE= }} | ||
===Crystal Structure of a PALB2 / BRCA2 complex=== | ===Crystal Structure of a PALB2 / BRCA2 complex=== | ||
{{ABSTRACT_PUBMED_19609323}} | |||
==Disease== | |||
[[http://www.uniprot.org/uniprot/PALB2_HUMAN PALB2_HUMAN]] Defects in PALB2 are a cause of susceptibility to breast cancer (BC) [MIM:[http://omim.org/entry/114480 114480]]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note=Breast cancer susceptibility is strongly associated with PALB2 truncating mutations. Conversely, rare missense mutations do not strongly influence breast cancer risk (PubMed:22241545). Defects in PALB2 are the cause of Fanconi anemia complementation group N (FANCN) [MIM:[http://omim.org/entry/610832 610832]]. It is a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.<ref>PMID:17200672</ref> Defects in PALB2 are the cause of pancreatic cancer type 3 (PNCA3) [MIM:[http://omim.org/entry/613348 613348]]. It is a malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.<ref>PMID:19264984</ref> [[http://www.uniprot.org/uniprot/BRCA2_HUMAN BRCA2_HUMAN]] Defects in BRCA2 are a cause of susceptibility to breast cancer (BC) [MIM:[http://omim.org/entry/114480 114480]]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.<ref>PMID:16793542</ref><ref>PMID:8640237</ref><ref>PMID:9150152</ref><ref>PMID:9654203</ref><ref>PMID:9609997</ref><ref>PMID:9971877</ref><ref>PMID:10399947</ref><ref>PMID:10978364</ref><ref>PMID:11139248</ref><ref>PMID:11241844</ref><ref>PMID:12145750</ref><ref>PMID:12373604</ref><ref>PMID:12442274</ref><ref>PMID:12442275</ref><ref>PMID:11948477</ref><ref>PMID:12938098</ref><ref>PMID:15026808</ref><ref>PMID:15172753</ref><ref>PMID:14722926</ref><ref>PMID:15365993</ref> Defects in BRCA2 are the cause of pancreatic cancer type 2 (PNCA2) [MIM:[http://omim.org/entry/613347 613347]]. It is a malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.<ref>PMID:9140390</ref> Defects in BRCA2 are a cause of susceptibility to familial breast-ovarian cancer type 2 (BROVCA2) [MIM:[http://omim.org/entry/612555 612555]]. A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate. Defects in BRCA2 are the cause of Fanconi anemia complementation group D type 1 (FANCD1) [MIM:[http://omim.org/entry/605724 605724]]. It is a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.<ref>PMID:12065746</ref><ref>PMID:14670928</ref><ref>PMID:16825431</ref> Defects in BRCA2 are a cause of glioma type 3 (GLM3) [MIM:[http://omim.org/entry/613029 613029]]. Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes.<ref>PMID:15689453</ref> | |||
==Function== | |||
[[http://www.uniprot.org/uniprot/PALB2_HUMAN PALB2_HUMAN]] Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks. Serves as the molecular scaffold in the formation of the BRCA1-PALB2-BRCA2 complex which is essential for homologous recombination. Strongly stimulates the DNA strand-invasion activity of RAD51, stabilizes the nucleoprotein filament against a disruptive BRC3-BRC4 polypeptide and helps RAD51 to overcome the suppressive effect of replication protein A (RPA). Functionally cooperates with RAD51AP1 in promoting of D-loop formation by RAD51. Essential partner of BRCA2 that promotes the localization and stability of BRCA2. Also enables its recombinational repair and checkpoint functions of BRCA2. May act by promoting stable association of BRCA2 with nuclear structures, allowing BRCA2 to escape the effects of proteasome-mediated degradation. Binds DNA with high affinity for D loop, which comprises single-stranded, double-stranded and branched DNA structures.<ref>PMID:16793542</ref><ref>PMID:19423707</ref><ref>PMID:19369211</ref><ref>PMID:20871615</ref><ref>PMID:20871616</ref> [[http://www.uniprot.org/uniprot/BRCA2_HUMAN BRCA2_HUMAN]] Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. In concert with NPM1, regulates centrosome duplication.<ref>PMID:15115758</ref><ref>PMID:15199141</ref><ref>PMID:15671039</ref><ref>PMID:18317453</ref><ref>PMID:20729859</ref><ref>PMID:20729858</ref><ref>PMID:20729832</ref><ref>PMID:21084279</ref> | |||
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==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
<ref group="xtra">PMID:019609323</ref><references group="xtra"/> | <ref group="xtra">PMID:019609323</ref><references group="xtra"/><references/> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Oliver, A W.]] | [[Category: Oliver, A W.]] | ||
