RAD51AP1 is a structure-specific DNA binding protein that stimulates joint molecule formation during RAD51-mediated homologous recombination.

Abstract:

:Homologous recombination is essential for preserving genome integrity. Joining of homologous DNA molecules through strand exchange, a pivotal step in recombination, is mediated by RAD51. Here, we identify RAD51AP1 as a RAD51 accessory protein that specifically stimulates joint molecule formation through the combination of structure-specific DNA binding and physical contact with RAD51. At the cellular level, we show that RAD51AP1 is required to protect cells from the adverse effects of DNA double-strand break-inducing agents. At the biochemical level, we show that RAD51AP1 has a selective affinity for branched-DNA structures that are obligatory intermediates during joint molecule formation. Our results highlight the importance of structural transitions in DNA as control points in recombination. The affinity of RAD51AP1 for the central protein and DNA intermediates of recombination confers on it the ability to control the preservation of genome integrity at a number of critical mechanistic steps.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Modesti M,Budzowska M,Baldeyron C,Demmers JA,Ghirlando R,Kanaar R

doi

10.1016/j.molcel.2007.08.025

subject

Has Abstract

pub_date

2007-11-09 00:00:00

pages

468-81

issue

3

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(07)00595-3

journal_volume

28

pub_type

杂志文章
  • Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites.

    abstract::Yeast histone H2A is phosphorylated on Ser129 upon DNA damage, an event required for efficient repair. We show that phosphorylation occurs rapidly over a large region around DNA double-strand breaks (DSBs). Histone H4 acetylation is also important for DSB repair, and we found that the NuA4 HAT complex associates speci...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2004.12.003

    authors: Downs JA,Allard S,Jobin-Robitaille O,Javaheri A,Auger A,Bouchard N,Kron SJ,Jackson SP,Côté J

    更新日期:2004-12-22 00:00:00

  • Accessibility of nucleosomal DNA to V(D)J cleavage is modulated by RSS positioning and HMG1.

    abstract::B and T cell receptor gene assembly by V(D)J recombination is tightly regulated during lymphoid development. The mechanisms involved in this regulation are poorly understood. Here we show that nucleosomal DNA is refractory to V(D)J cleavage. However, the presence of HMG1, a chromatin-associated nonhistone DNA-binding ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(00)80297-x

    authors: Kwon J,Imbalzano AN,Matthews A,Oettinger MA

    更新日期:1998-12-01 00:00:00

  • Bax exists in a dynamic equilibrium between the cytosol and mitochondria to control apoptotic priming.

    abstract::The proapoptotic Bcl-2 protein Bax is predominantly found in the cytosol of nonapoptotic cells and is commonly thought to translocate to mitochondria following an apoptotic stimulus. The current model for Bax activation is that BH3 proteins bind to cytosolic Bax, initiating mitochondrial targeting and outer-membrane p...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2012.12.022

    authors: Schellenberg B,Wang P,Keeble JA,Rodriguez-Enriquez R,Walker S,Owens TW,Foster F,Tanianis-Hughes J,Brennan K,Streuli CH,Gilmore AP

    更新日期:2013-03-07 00:00:00

  • PRDM16 Suppresses MLL1r Leukemia via Intrinsic Histone Methyltransferase Activity.

    abstract::PRDM16 is a transcription co-factor that plays critical roles in development of brown adipose tissue, as well as maintenance of adult hematopoietic and neural stem cells. Here we report that PRDM16 is a histone H3K4 methyltransferase on chromatin. Mutation in the N-terminal PR domain of PRDM16 abolishes the intrinsic ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.03.010

    authors: Zhou B,Wang J,Lee SY,Xiong J,Bhanu N,Guo Q,Ma P,Sun Y,Rao RC,Garcia BA,Hess JL,Dou Y

    更新日期:2016-04-21 00:00:00

  • The N-terminal domain of Nup159 forms a beta-propeller that functions in mRNA export by tethering the helicase Dbp5 to the nuclear pore.

    abstract::Nuclear export of mRNA in eukaryotic cells is mediated by soluble transport factors and components of the nuclear pore complex (NPC). The cytoplasmically oriented nuclear pore protein Nup159 plays a critical role in mRNA export through its conserved N-terminal domain (NTD). Here, we report the crystal structure of the...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2004.10.032

    authors: Weirich CS,Erzberger JP,Berger JM,Weis K

    更新日期:2004-12-03 00:00:00

  • An AAA Motor-Driven Mechanical Switch in Rpn11 Controls Deubiquitination at the 26S Proteasome.

    abstract::Poly-ubiquitin chains direct protein substrates to the 26S proteasome, where they are removed by the deubiquitinase Rpn11 during ATP-dependent substrate degradation. Rapid deubiquitination is required for efficient degradation but must be restricted to committed substrates that are engaged with the ATPase motor to pre...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2017.07.023

    authors: Worden EJ,Dong KC,Martin A

    更新日期:2017-09-07 00:00:00

  • A Conserved Kinase-Based Body-Temperature Sensor Globally Controls Alternative Splicing and Gene Expression.

    abstract::Homeothermic organisms maintain their core body temperature in a narrow, tightly controlled range. Whether and how subtle circadian oscillations or disease-associated changes in core body temperature are sensed and integrated in gene expression programs remain elusive. Furthermore, a thermo-sensor capable of sensing t...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2020.01.028

    authors: Haltenhof T,Kotte A,De Bortoli F,Schiefer S,Meinke S,Emmerichs AK,Petermann KK,Timmermann B,Imhof P,Franz A,Loll B,Wahl MC,Preußner M,Heyd F

    更新日期:2020-04-02 00:00:00

  • A BLAST from the past: ancient origin of human Sm proteins.

    abstract::In this issue of Molecular Cell, Zhang et al. and Møller et al. independently report studies of the E. coli Hfq protein, revealing significant sequence similarities with human Sm proteins. Their findings suggest that Hfq, and the Sm and Sm-like (Lsm) proteins, may function in stabilizing interactions between RNA molec...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/s1097-2765(02)00429-x

    authors: Donahue WF,Jarrell KA

    更新日期:2002-01-01 00:00:00

  • Late S phase-specific recruitment of Mre11 complex triggers hierarchical assembly of telomere replication proteins in Saccharomyces cerevisiae.

    abstract::In Saccharomyces cerevisiae, telomere replication occurs in late S phase and is accompanied by dynamic remodeling of its protein components. Here, we show that MRX (Mre11-Rad50-Xrs2), an evolutionarily conserved protein complex involved in DNA double-strand break (DSB) repair, is recruited to the telomeres in late S p...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2005.01.014

    authors: Takata H,Tanaka Y,Matsuura A

    更新日期:2005-02-18 00:00:00

  • Dynamic RNA modifications in posttranscriptional regulation.

    abstract::Cellular RNAs can be chemically modified over a hundred different ways. These modifications were once thought to be static, discrete, and utilized to fine-tune RNA structure and function. However, recent studies have revealed that some modifications, like mRNA methylation, can be reversed, and these reversible modific...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2014.09.001

    authors: Wang X,He C

    更新日期:2014-10-02 00:00:00

  • APC is essential for targeting phosphorylated beta-catenin to the SCFbeta-TrCP ubiquitin ligase.

    abstract::Ubiquitin-dependent proteolysis is an important mechanism that suppresses the beta-catenin transcription factor in cells without Wnt stimulation. A critical step in this regulatory pathway is to create a SCF(beta-TrCP) E3 ubiquitin ligase binding site for beta-catenin. Here we show that the SCF(beta-TrCP) binding site...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2008.10.023

    authors: Su Y,Fu C,Ishikawa S,Stella A,Kojima M,Shitoh K,Schreiber EM,Day BW,Liu B

    更新日期:2008-12-05 00:00:00

  • Stalled fork rescue via dormant replication origins in unchallenged S phase promotes proper chromosome segregation and tumor suppression.

    abstract::Eukaryotic cells license far more origins than are actually used for DNA replication, thereby generating a large number of dormant origins. Accumulating evidence suggests that such origins play a role in chromosome stability and tumor suppression, though the underlying mechanism is largely unknown. Here, we show that ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.02.006

    authors: Kawabata T,Luebben SW,Yamaguchi S,Ilves I,Matise I,Buske T,Botchan MR,Shima N

    更新日期:2011-03-04 00:00:00

  • The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility.

    abstract::During meiosis, the homologous chromosomes pair and recombine. An evolutionarily conserved protein structure, the synaptonemal complex (SC), is located along the paired meiotic chromosomes. We have studied the function of a structural component in the axial/lateral element of the SC, the synaptonemal complex protein 3...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(00)80404-9

    authors: Yuan L,Liu JG,Zhao J,Brundell E,Daneholt B,Höög C

    更新日期:2000-01-01 00:00:00

  • The Kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1 activation by suppressing PP5.

    abstract::Reactive oxygen species (ROS)-induced activation of Apoptosis signal-regulating kinase 1 (ASK1) plays crucial roles in oxidative stress-mediated cell death through the activation of the JNK and p38 MAPK pathways. However, the regulatory mechanism of ASK1 in the oxidative stress response remains to be elucidated. Here,...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2012.09.018

    authors: Sekine Y,Hatanaka R,Watanabe T,Sono N,Iemura S,Natsume T,Kuranaga E,Miura M,Takeda K,Ichijo H

    更新日期:2012-12-14 00:00:00

  • hnRNP A1 proofreads 3' splice site recognition by U2AF.

    abstract::One of the earliest steps in metazoan pre-mRNA splicing involves binding of U2 snRNP auxiliary factor (U2AF) 65 KDa subunit to the polypyrimidine (Py) tract and of the 35 KDa subunit to the invariant AG dinucleotide at the intron 3' end. Here we use in vitro and in vivo depletion, as well as reconstitution assays usin...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.11.033

    authors: Tavanez JP,Madl T,Kooshapur H,Sattler M,Valcárcel J

    更新日期:2012-02-10 00:00:00

  • Functional proteomics identifies targets of phosphorylation by B-Raf signaling in melanoma.

    abstract::Melanoma and other cancers harbor oncogenic mutations in the protein kinase B-Raf, which leads to constitutive activation and dysregulation of MAP kinase signaling. In order to elucidate molecular determinants responsible for B-Raf control of cancer phenotypes, we present a method for phosphoprotein profiling, using n...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2009.03.007

    authors: Old WM,Shabb JB,Houel S,Wang H,Couts KL,Yen CY,Litman ES,Croy CH,Meyer-Arendt K,Miranda JG,Brown RA,Witze ES,Schweppe RE,Resing KA,Ahn NG

    更新日期:2009-04-10 00:00:00

  • Condensin: The Little Motor Protein that Could.

    abstract::Kong et al. (2020) present the low-resolution structure of the ATPɣS-bound human condensin I and II complexes and demonstrate that human condensins can extrude DNA loops in a symmetric and asymmetric fashion and compact nucleosome-bound DNA. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2020.06.025

    authors: Goloborodko A

    更新日期:2020-07-02 00:00:00

  • Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs.

    abstract::Posttranslational histone modifications participate in modulating the structure and function of chromatin. Promoters of transcribed genes are enriched with K4 trimethylation and hyperacetylation on the N-terminal tail of histone H3. Recently, PHD finger proteins, like Yng1 in the NuA3 HAT complex, were shown to intera...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2006.10.026

    authors: Taverna SD,Ilin S,Rogers RS,Tanny JC,Lavender H,Li H,Baker L,Boyle J,Blair LP,Chait BT,Patel DJ,Aitchison JD,Tackett AJ,Allis CD

    更新日期:2006-12-08 00:00:00

  • A bidirectional origin of replication maps to the major noncoding region of human mitochondrial DNA.

    abstract::In solid tissues of vertebrates, initiation of mitochondrial DNA replication encompasses a broad zone downstream of the major noncoding region (NCR). In contrast, analysis with two-dimensional agarose gel electrophoresis of mitochondrial DNA replication intermediates in cultured human cells revealed initiation concent...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2005.05.002

    authors: Yasukawa T,Yang MY,Jacobs HT,Holt IJ

    更新日期:2005-06-10 00:00:00

  • HATs off to PIC assembly.

    abstract::There are many regulated steps in the assembly of a transcription preinitiation complex (PIC). In this issue of Molecular Cell, Black et. al. (2006) reveal a catalytic switch mechanism in which autoacetylation of the HAT p300 triggers its dissociation from a promoter in a manner that is coupled to TFIID association. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章,评审

    doi:10.1016/j.molcel.2006.08.022

    authors: Pugh BF

    更新日期:2006-09-15 00:00:00

  • Prolyl cis-trans Isomerization as a molecular timer in Crk signaling.

    abstract::In a recent issue of Molecular Cell, use NMR to identify peptidyl-prolyl cis-trans isomerization as an autoinhibitory switch in the adaptor protein Crk, suggesting a new mechanism for controlling the rate of formation of signaling complexes. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2007.02.005

    authors: Nicholson LK,Lu KP

    更新日期:2007-02-23 00:00:00

  • Calmodulin-dependent activation of MAP kinase for ROS homeostasis in Arabidopsis.

    abstract::Rapid recognition and signal transduction of mechanical wounding through various signaling molecules, including calcium (Ca²+), protein phosphorylation, and reactive oxygen species (ROS), are necessary early events leading to stress resistance in plants. Here we report that an Arabidopsis mitogen-activated protein kin...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.02.029

    authors: Takahashi F,Mizoguchi T,Yoshida R,Ichimura K,Shinozaki K

    更新日期:2011-03-18 00:00:00

  • Detection of high-affinity and sliding clamp modes for MSH2-MSH6 by single-molecule unzipping force analysis.

    abstract::Mismatch repair (MMR) is initiated by MutS family proteins (MSH) that recognize DNA mismatches and recruit downstream repair factors. We used a single-molecule DNA-unzipping assay to probe interactions between S. cerevisiae MSH2-MSH6 and a variety of DNA mismatch substrates. This work revealed a high-specificity bindi...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2005.10.014

    authors: Jiang J,Bai L,Surtees JA,Gemici Z,Wang MD,Alani E

    更新日期:2005-12-09 00:00:00

  • Too much of a good thing: the Prl-3 in p53's oyster.

    abstract::In this issue of Molecular Cell, Basak et al. (2008) identify Prl-3 as a p53-inducible gene acting in DNA damage-induced cell-cycle arrest. Both deletion and overexpression of Prl-3 can be cytostatic, adding to a growing list of genes whose expression must be carefully titrated for proper cell proliferation. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2008.04.006

    authors: Hinds PW

    更新日期:2008-05-09 00:00:00

  • Insights into FlaI functions in archaeal motor assembly and motility from structures, conformations, and genetics.

    abstract::Superfamily ATPases in type IV pili, type 2 secretion, and archaella (formerly archaeal flagella) employ similar sequences for distinct biological processes. Here, we structurally and functionally characterize prototypical superfamily ATPase FlaI in Sulfolobus acidocaldarius, showing FlaI activities in archaeal swimmi...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2013.01.014

    authors: Reindl S,Ghosh A,Williams GJ,Lassak K,Neiner T,Henche AL,Albers SV,Tainer JA

    更新日期:2013-03-28 00:00:00

  • A Therapeutic Double Whammy: Transcriptional or Post-transcriptional Suppression of Microsatellite Repeat Toxicity by Cas9.

    abstract::Microsatellite expansion diseases are caused by unstable tandem repeats of 3-10 nucleotides that become pathogenic beyond a threshold number of copies. Two groups present different approaches to reduce pathogenesis by targeting deactivated Cas9 to either the DNA (Pinto et al., 2017) or the RNA (Batra et al., 2017) rep...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2017.10.023

    authors: Rao AN,Cooper TA

    更新日期:2017-11-02 00:00:00

  • Replicational Dilution of H3K27me3 in Mammalian Cells and the Role of Poised Promoters.

    abstract::Polycomb repressive complex 2 (PRC2) places H3K27me3 at developmental genes and is causally implicated in keeping bivalent genes silent. It is unclear if that silence requires minimum H3K27me3 levels and how the mark transmits faithfully across mammalian somatic cell generations. Mouse intestinal cells lacking EZH2 me...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2020.01.017

    authors: Jadhav U,Manieri E,Nalapareddy K,Madha S,Chakrabarti S,Wucherpfennig K,Barefoot M,Shivdasani RA

    更新日期:2020-04-02 00:00:00

  • Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation.

    abstract::Conjugation of ubiquitin-like protein Nedd8 to cullins (neddylation) is essential for the function of cullin-RING ubiquitin ligases (CRLs). Here, we show that neddylation stimulates CRL activity by multiple mechanisms. For the initiator ubiquitin, the major effect is to bridge the approximately 50 A gap between naked ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2008.08.021

    authors: Saha A,Deshaies RJ

    更新日期:2008-10-10 00:00:00

  • Missing the Mark: PRDM9-Dependent Methylation Is Required for Meiotic DSB Targeting.

    abstract::PRDM9 determines the localization of meiotic recombination hotspots, which are associated with histone H3 methylation. It is not known whether PRDM9's methyltransferase activity is required or how some PRDM9 alleles can dominate the distribution of hotspots over other alleles. Diagouraga, Clément, and colleagues (2018...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2018.02.021

    authors: Kang R,Zelazowski MJ,Cole F

    更新日期:2018-03-01 00:00:00

  • Human origins of DNA replication selected from a library of nascent DNA.

    abstract::The identification of metazoan origins of DNA replication has so far been hampered by the lack of a suitable genetic screening and by the cumbersomeness of the currently available mapping procedures. Here we describe the construction of a library of nascent DNA, representative of all cellular origin sequences, and its...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2005.07.005

    authors: Todorovic V,Giadrossi S,Pelizon C,Mendoza-Maldonado R,Masai H,Giacca M

    更新日期:2005-08-19 00:00:00