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Open AccessJournal ArticleDOI

RVBs are required for assembling a functional TIP60 complex.

TLDR
RuvBL1/RVB2 proteins act as molecular adaptors that can substitute for one another to facilitate the optimal assembly, heat stability, and function of the TIP60 complex.
Abstract
RVB1/RVB2 (RuvBL1/RuvBL2 or pontin/reptin) are enigmatic AAA+ ATPase proteins that are present in multiple cellular complexes. Although they have been implicated in many cellular functions, the exact molecular function of RVB proteins in the various complexes is not clear. TIP60 complex (TIP60.com) is a tumor suppressor chromatin-remodeling complex containing RVB proteins. RVBs are required for the lysine acetyltransferase activity of TIP60.com but not for that of the pure recombinant TIP60 polypeptide. Here we describe two molecular functions of RVBs in TIP60.com. First, RVBs negate the repression of catalytic activity of TIP60 by another protein in TIP60.com, p400. RVBs competitively displace the SNF2 domain of p400 from the TIP60 polypeptide. In addition RVBs are also required for heat stability of TIP60.com by a p400-independent pathway. RVB1 and RVB2 are redundant with each other for these functions and do not require their ATPase activities. Thus, RVB proteins act as molecular adaptors that can substitute for one another to facilitate the optimal assembly, heat stability, and function of the TIP60 complex.

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PRMTs and Arginine Methylation: Cancer’s Best-Kept Secret?

TL;DR: This review focuses on advances made regarding the role of PRMTs in stem cell biology, epigenetics, splicing, immune surveillance and the DNA damage response, and highlights the rapid rise of specific inhibitors that are now in clinical trials for cancer therapy.
Journal ArticleDOI

PRMT5-Dependent Methylation of the TIP60 Coactivator RUVBL1 Is a Key Regulator of Homologous Recombination

TL;DR: The findings reveal the importance of PRMT5-mediated arginine methylation during DSB repair pathway choice through its ability to regulate acetylation-dependent control of 53BP1 localization.
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The Role of Pontin and Reptin in Cellular Physiology and Cancer Etiology

TL;DR: Pontin and Reptin are highly conserved ATPases of the AAA+ superfamily and are involved in various cellular processes that are important for oncogenesis and are also current targets for the development of new therapeutic anticancer drugs.
Journal ArticleDOI

Patching Broken DNA: Nucleosome Dynamics and the Repair of DNA Breaks

TL;DR: The nucleosome surface may function as a central hub during DSB repair, directing specific patterns of histone modification, recruiting DNA repair proteins and modulating chromatin packing during processing of the damaged DNA template.
Journal ArticleDOI

The tale of a tail: histone H4 acetylation and the repair of DNA breaks.

TL;DR: How the H4 tail functions as a dynamic hub that can be programmed through acetylation to alter chromatin packing and recruit repair proteins to the break site is discussed.
References
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Journal ArticleDOI

ATP-Driven Exchange of Histone H2AZ Variant Catalyzed by SWR1 Chromatin Remodeling Complex

TL;DR: It is found that Swr1, a Swi2/Snf2-related adenosine triphosphatase, is the catalytic core of a multisubunit, histone-variant exchanger that efficiently replaces conventional histone H2A with hist one H2AZ in nucleosome arrays.
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Involvement of the tip60 histone acetylase complex in dna repair and apoptosis

TL;DR: Results indicate that the histone acetylase TIP60-containing complex plays a role in DNA repair and apoptosis, suggesting a defect in the cells' ability to signal the existence of DNA damage to the apoptotic machinery.
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A chromatin remodelling complex involved in transcription and DNA processing

TL;DR: Results indicate that chromatin remodelling driven by the Ino80 ATPase may be connected to transcription as well as DNA damage repair.
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A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM

TL;DR: It is demonstrated that DNA damage induces the rapid acetylation of ATM and the Tip60 HAT plays a key role in the activation of ATM's kinase activity in response to DNA damage.
Journal ArticleDOI

Acetylation by Tip60 Is Required for Selective Histone Variant Exchange at DNA Lesions

TL;DR: It is demonstrated that the Drosophila Tip60 (dTip60) chromatin-remodeling complex acetylates nucleosomal phospho-H2Av and exchanges it with an unmodified H2Av, revealing a previously unknown mechanism for selective histone exchange that uses the concerted action of two distinct Chromatin-Remodeling enzymes within the same multiprotein complex.
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