| RRC ID |
3390
|
| 著者 |
Martin JS, Winkelmann N, Petalcorin MI, McIlwraith MJ, Boulton SJ.
|
| タイトル |
RAD-51-dependent and -independent roles of a Caenorhabditis elegans BRCA2-related protein during DNA double-strand break repair.
|
| ジャーナル |
Mol Cell Biol
|
| Abstract |
The BRCA2 tumor suppressor is implicated in DNA double-strand break (DSB) repair by homologous recombination (HR), where it regulates the RAD51 recombinase. We describe a BRCA2-related protein of Caenorhabditis elegans (CeBRC-2) that interacts directly with RAD-51 via a single BRC motif and that binds preferentially to single-stranded DNA through an oligonucleotide-oligosaccharide binding fold. Cebrc-2 mutants fail to repair meiotic or radiation-induced DSBs by HR due to inefficient RAD-51 nuclear localization and a failure to target RAD-51 to sites of DSBs. Genetic and cytological comparisons of Cebrc-2 and rad-51 mutants revealed fundamental phenotypic differences that suggest a role for Cebrc-2 in promoting the use of an alternative repair pathway in the absence of rad-51 and independent of nonhomologous end joining (NHEJ). Unlike rad-51 mutants, Cebrc-2 mutants also accumulate RPA-1 at DSBs, and abnormal chromosome aggregates that arise during the meiotic prophase can be rescued by blocking the NHEJ pathway. CeBRC-2 also forms foci in response to DNA damage and can do so independently of rad-51. Thus, CeBRC-2 not only regulates RAD-51 during HR but can also function independently of rad-51 in DSB repair processes.
|
| 巻・号 |
25(8)
|
| ページ |
3127-39
|
| 公開日 |
2005-4-1
|
| DOI |
10.1128/MCB.25.8.3127-3139.2005
|
| PII |
25/8/3127
|
| PMID |
15798199
|
| PMC |
PMC1069622
|
| MeSH |
Amino Acid Motifs
Amino Acid Sequence
Animals
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism
Caenorhabditis elegans / physiology*
Caenorhabditis elegans Proteins
DNA / radiation effects
DNA Damage*
DNA Repair / physiology*
DNA-Binding Proteins / analysis
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
DNA-Binding Proteins / physiology*
Embryo, Nonmammalian
Gene Deletion
Genes, Lethal
Germ Cells / chemistry
Germ Cells / metabolism
Germ Cells / radiation effects
Molecular Sequence Data
Rad51 Recombinase
Replication Protein A
|
| IF |
3.611
|
| 引用数 |
108
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| 線虫 |
tm1086 |
