The BRCA2-Interacting Protein DSS1 Is Vital for DNA Repair, Recombination, and Genome Stability in Ustilago maydis

Kojic, Milorad; Yang, Hao‐Xian; Kostrub, Corwin F.; Pavletich, Nikola P.; Holloman, William K.

doi:10.1016/s1097-2765(03)00367-8

Cited by 110 publications

(125 citation statements)

References 25 publications

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“…In contrast, certain combined domains of BRCA2 promote Rad51-mediated strand exchange in vitro, suggesting that there may be intramolecular collaboration between distinct domains of BRCA2 [140,161]. The U. maydis BRCA2 homolog, Brh2, possesses only one BRC domain and has been purified with DSS1 in vitro [20,25,141]. Brh2/DSS1 efficiently catalyzes the loading of Rad51 onto the free 5′ end of a dsDNA-ssDNA junction, provided that the ssDNA is pre-coated with RPA (as it would be in vivo).…”

Section: Molecular Functions Of Brca1 and Brca2mentioning

confidence: 99%

Minding the gap: The underground functions of BRCA1 and BRCA2 at stalled replication forks

Nagaraju

Scully

2007

DNA Repair

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The hereditary breast and ovarian cancer predisposition genes, BRCA1 and BRCA2, participate in the repair of DNA double strand breaks by homologous recombination. Circumstantial evidence implicates these genes in recombinational responses to DNA polymerase stalling during the S phase of the cell cycle. These responses play a key role in preventing genomic instability and cancer. Here, we review the current literature implicating the BRCA pathway in HR at stalled replication forks and explore the hypothesis that BRCA1 and BRCA2 participate in the recombinational resolution of single stranded DNA lesions termed "daughter strand gaps", generated during replication across a damaged DNA template.

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Section: Molecular Functions Of Brca1 and Brca2mentioning

confidence: 99%

Minding the gap: The underground functions of BRCA1 and BRCA2 at stalled replication forks

Nagaraju

Scully

2007

DNA Repair

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“…Interestingly, a DSS1 ortholog in Ustilago maydis has been found to associate with a BRCA2-related protein, Brh2 (Kojic et al, 2003). Deletion of DSS1 from U. maydis has been shown to result in radiation hypersensitivity, recombination deficiency, meiosis defect, and genomic instability, similar to the phenotype of Brh2 and Rad51 deletion in U. maydis (Kojic et al, 2003). In addition, the yeast ortholog of DSS1, sem1p, regulates exocytosis and pseudohyphal differentiation (Jantti et al, 1999).…”

Section: Introductionmentioning

confidence: 96%

DSS1 is required for the stability of BRCA2

et al. 2005

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DSS1 is an evolutionarily conserved acidic protein that binds to BRCA2. However, study of the function of DSS1 in mammalian cells has been hampered because endogenous DSS1 has not been detectable by Western blotting. Here, we developed a modified Western blotting protocol that detects endogenous DSS1 protein, and used it to study the function of DSS1 and its interaction with BRCA2 in mammalian cells. We found that essentially all BRCA2 in human cell lines is associated with DSS1. Importantly, we found that RNAi knockdown of DSS1 in human cell lines led to dramatic loss of BRCA2 protein, mainly due to its increased degradation. Furthermore, the stability of BRCA2 mutant devoid of the DSS1-binding domain is unaffected by the depletion of DSS1. Most notably, like BRCA2 depletion, DSS1 depletion also led to hypersensitivity to DNA damage. These results demonstrated that the stability of BRCA2 protein in mammalian cells depends on the presence of DSS1. Deletion or mutation of DSS1 or suppression of its expression by other mechanisms are therefore potential causative mechanisms for human breast and ovarian cancer. Such mechanisms may be relevant to sporadic as well as familiar breast cancer where BRCA1 and BRCA2 mutations are not present.

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“…While Brca2 was known to localize on the meiotic chromosomes during the formation of the synaptonemal complex in human (Chen et al, 1998a), the interaction disclosed between Brca2 and Dmc1 in Arabidopsis (Arabidopsis thaliana) helped assign a role for Brca2 at meiosis (Siaud et al, 2004). Another interactant of Brca2, Dss1, was uncovered (Marston et al, 1999), the depletion of which leads to a brca2-like phenotype in Ustilago or mouse (Kojic et al, 2003;Gudmundsdottir et al, 2004). Its yeast (Saccharomyces cerevisiae) counterpart, Sem1, is found associated with the 19S proteasome, but it also participates in the resistance to genotoxic treatment (Funakoshi et al, 2004;Krogan et al, 2004), although no Brca2-like protein can be identified in yeast.…”

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confidence: 99%

Interaction between Arabidopsis Brca2 and Its Partners Rad51, Dmc1, and Dss1

et al. 2006

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The Arabidopsis (Arabidopsis thaliana) orthologs of Brca2, a protein whose mutations are involved in breast cancer in humans, were previously shown to be essential at meiosis. In an attempt to better understand the Brca2-interacting properties, we examined four partners of the two isoforms of Brca2 identified in Arabidopsis (AtRad51, AtDmc1, and two AtDss1 isoforms). The two Brca2 and the two Dss1 isoforms are named AtBrca2(IV), AtBrca2(V), AtDss1(I), and AtDss1(V) after their chromosomal localization. We first show that both AtBrca2 proteins can interact with either AtRad51 or AtDmc1 in vitro, and that the N-terminal region of AtBrca2 is responsible for these interactions. More specifically, the BRC motifs (so called because iterated in the Brca2 protein) in Brca2 are involved in these interactions: BRC motif number 2 (BRC2) alone can interact with AtDmc1, whereas BRC motif number 4 (BRC4) recognizes AtRad51. The human Rad51 and Dmc1 proteins themselves can interact with either the complete (HsRad51) or a shorter version of AtBrca2 (HsRad51 or HsDmc1) that comprises all four BRC motifs. We also identified two Arabidopsis isoforms of Dss1, another known partner of Brca2 in other organisms. Although all four Brca2 and Dss1 proteins are much conserved, AtBrca2(IV) interacts with only one of these AtDss1 proteins, whereas AtBrca2(V) interacts with both of them. Finally, we show for the first time that an AtBrca2 protein could bind two different partners at the same time: AtRad51 and AtDss1(I), or AtDmc1 and AtDss1(I).

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The BRCA2-Interacting Protein DSS1 Is Vital for DNA Repair, Recombination, and Genome Stability in Ustilago maydis

Cited by 110 publications

References 25 publications

Minding the gap: The underground functions of BRCA1 and BRCA2 at stalled replication forks

Minding the gap: The underground functions of BRCA1 and BRCA2 at stalled replication forks

DSS1 is required for the stability of BRCA2

Interaction between Arabidopsis Brca2 and Its Partners Rad51, Dmc1, and Dss1

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