Mutation of lysine-48 to arginine in the yeast RAD3 protein abolishes its ATPase and DNA helicase activities but not the ability to bind ATP.

Sung, Patrick; Higgins, David R.; Prakash, Louise; Prakash, Satya

doi:10.1002/j.1460-2075.1988.tb03193.x

Cited by 262 publications

(236 citation statements)

References 55 publications

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“…A mutant form of BACH1 (K52R) predicted to be enzymatically inactive (6) was generated in parallel. This conserved residue, when mutated in the XPD and ChlR1 helicases, rendered these proteins inactive (18)(19)(20). This same BACH1 mutation disrupted BRCA1-mediated DSBR (6).…”

Section: Resultsmentioning

confidence: 95%

The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations

Cantor

Drapkin²,

Zhang³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

219

247

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BACH1 is a nuclear protein that directly interacts with the highly conserved, C-terminal BRCT repeats of the tumor suppressor, BRCA1. Mutations within the BRCT repeats disrupt the interaction between BRCA1 and BACH1, lead to defects in DNA repair, and result in breast and ovarian cancer. BACH1 is necessary for efficient double-strand break repair in a manner that depends on its association with BRCA1. Moreover, some women with early-onset breast cancer and no abnormalities in either BRCA1 or BRCA2 carry germline BACH1 coding sequence changes, suggesting that abnormal BACH1 function contributes to tumor induction. Here, we show that BACH1 is both a DNA-dependent ATPase and a 5′-to-3′ DNA helicase. In two patients with early-onset breast cancer who carry distinct germline BACH1 coding sequence changes, the resulting proteins are defective in helicase activity, indicating that these sequence changes disrupt protein function. These results reinforce the notion that mutant BACH1 participates in breast cancer development

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Section: Resultsmentioning

confidence: 95%

The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations

Cantor

Drapkin²,

Zhang³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

219

247

View full text Add to dashboard Cite

show abstract

“…Indeed, no interaction could be observed when the AAA domain was deleted (DN-Atad2, Figure 4c, compare lanes 4-2 and 8-6). Moreover, a single amino acid change in the Walker A motif of the AAA domain (MtA-Atad2), known to disrupt the binding of ATP in other AAA ATPases (Sung et al, 1988;Rubin et al, 1998), also alleviates its interaction with Flag-Atad2 Wt (Figure 4c, lane 10). Interestingly, the deletion of amino acids 823-1040 of Atad2-S diminishes the interaction of Atad2-S with itself, suggesting that its C-terminal part could be required for the stabilization of Atad2-S multimers ( Figure 4c, compare lanes 6 and 2).…”

Section: Targeting Of Ach4 By the Multimeric Form Of Atad2mentioning

confidence: 99%

Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers

et al. 2010

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Cancer cells frequently express genes normally active in male germ cells. ATAD2 is one of them encoding a conserved factor harbouring an AAA type ATPase domain and a bromodomain. We show here that ATAD2 is highly expressed in testis as well as in many cancers of different origins and that its high expression is a strong predictor of rapid mortality in lung and breast cancers. These observations suggest that ATAD2 acts on upstream and basic cellular processes to enhance oncogenesis in a variety of unrelated cell types. Accordingly, our functional studies show that ATAD2 controls chromatin dynamics, genome transcriptional activities and apoptotic cell response. We could also highlight some of the important intrinsic properties of its two regulatory domains, including a functional cross-talk between the AAA ATPase domain and the bromodomain. Altogether, these data indicate that ATAD2 overexpression in somatic cells, by acting on basic properties of chromatin, may contribute to malignant transformation.

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“…The catalytic activity of Rrm3p is needed for telomere replication DNA helicases can be multifunctional, having activities in addition to the unwinding of duplex DNA (see, e.g., Sung et al 1988;Formosa and Nittis 1999). To determine if the ATPase/helicase activity of Rrm3p is needed for replication of telomeric DNA, we used an RRM3 allele in which the invariant lysine in the ATP-binding pocket was mutated to alanine (K260A; Ivessa et al 2000).…”

Section: Replication Forks Slow As They Move Through the Chromosome Vmentioning

confidence: 99%

Saccharomyces Rrm3p, a 5′ to 3′ DNA helicase that promotes replication fork progression through telomeric and subtelomeric DNA

et al. 2002

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In wild-type Saccharomyces cerevisiae, replication forks slowed during their passage through telomeric C1–3A/TG1–3 tracts. This slowing was greatly exacerbated in the absence of RRM3, shown here to encode a 5′ to 3′ DNA helicase. Rrm3p-dependent fork progression was seen at a modified Chromosome VII-L telomere, at the natural X-bearing Chromosome III-L telomere, and at Y‘-bearing telomeres. Loss of Rrm3p also resulted in replication fork pausing at specific sites in subtelomeric DNA, such as at inactive replication origins, and at internal tracts of C1–3A/TG1–3 DNA. The ATPase/helicase activity of Rrm3p was required for its role in telomeric and subtelomeric DNA replication. Because Rrm3p was telomere-associated in vivo, it likely has a direct role in telomere replication.

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Mutation of lysine-48 to arginine in the yeast RAD3 protein abolishes its ATPase and DNA helicase activities but not the ability to bind ATP.

Cited by 262 publications

References 55 publications

The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations

The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations

Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers

Saccharomyces Rrm3p, a 5′ to 3′ DNA helicase that promotes replication fork progression through telomeric and subtelomeric DNA

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