FANCM and FAAP24 function in ATR-mediated checkpoint signaling independently of the Fanconi anemia core complex.


:The Fanconi anemia (FA) pathway is implicated in DNA repair and cancer predisposition. Central to this pathway is the FA core complex, which is targeted to chromatin by FANCM and FAAP24 following replication stress. Here we show that FANCM and FAAP24 interact with the checkpoint protein HCLK2 independently of the FA core complex. In addition to defects in FA pathway activation, downregulation of FANCM or FAAP24 also compromises ATR/Chk1-mediated checkpoint signaling, leading to defective Chk1, p53, and FANCE phosphorylation; 53BP1 focus formation; and Cdc25A degradation. As a result, FANCM and FAAP24 deficiency results in increased endogenous DNA damage and a failure to efficiently invoke cell-cycle checkpoint responses. Moreover, we find that the DNA translocase activity of FANCM, which is dispensable for FA pathway activation, is required for its role in ATR/Chk1 signaling. Our data suggest that DNA damage recognition and remodeling activities of FANCM and FAAP24 cooperate with ATR/Chk1 to promote efficient activation of DNA damage checkpoints.


Mol Cell


Molecular cell


Collis SJ,Ciccia A,Deans AJ,Horejsí Z,Martin JS,Maslen SL,Skehel JM,Elledge SJ,West SC,Boulton SJ




Has Abstract


2008-11-07 00:00:00














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    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Sablin EP,Krylova IN,Fletterick RJ,Ingraham HA

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    journal_title:Molecular cell

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    authors: Xue Z,Yuan H,Guo J,Liu Y

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    authors: Zhang Y,Shishkin AA,Nishida Y,Marcinkowski-Desmond D,Saini N,Volkov KV,Mirkin SM,Lobachev KS

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    authors: Margottin F,Bour SP,Durand H,Selig L,Benichou S,Richard V,Thomas D,Strebel K,Benarous R

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    pub_type: 杂志文章


    authors: Soelaiman S,Jakes K,Wu N,Li C,Shoham M

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    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Heuck AP,Hotze EM,Tweten RK,Johnson AE

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  • Advances in CLIP Technologies for Studies of Protein-RNA Interactions.

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    authors: Lee FCY,Ule J

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    authors: Capdevila J,Tsukui T,Rodríquez Esteban C,Zappavigna V,Izpisúa Belmonte JC

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    authors: Hoek TA,Khuperkar D,Lindeboom RGH,Sonneveld S,Verhagen BMP,Boersma S,Vermeulen M,Tanenbaum ME

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    authors: Stampouloglou E,Varelas X

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    authors: Berezikov E,Chung WJ,Willis J,Cuppen E,Lai EC

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    journal_title:Molecular cell

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    authors: Aizawa Y,Xiang Q,Lambowitz AM,Pyle AM

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    authors: Chen LY,Lingner J

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    journal_title:Molecular cell

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    authors: Bihani T,Hinds PW

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    authors: Garami A,Zwartkruis FJ,Nobukuni T,Joaquin M,Roccio M,Stocker H,Kozma SC,Hafen E,Bos JL,Thomas G

    更新日期:2003-06-01 00:00:00

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    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Torlai Triglia E,Rito T,Pombo A

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    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

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    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Fei J,Kosuri P,MacDougall DD,Gonzalez RL Jr

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  • RNA Structure Switches RBP Binding.

    abstract::RNA sequence motifs are not sufficient for association with RBPs. In this issue of Molecular Cell, Taliaferro et al. (2016) demonstrate that, other than sequence motif, RNA secondary structure plays a repressive role on RBP binding, both in vitro and in vivo. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Luo Z,Yang Q,Yang L

    更新日期:2016-10-20 00:00:00

  • An Atlas of Human Glycosylation Pathways Enables Display of the Human Glycome by Gene Engineered Cells.

    abstract::The structural diversity of glycans on cells-the glycome-is vast and complex to decipher. Glycan arrays display oligosaccharides and are used to report glycan hapten binding epitopes. Glycan arrays are limited resources and present saccharides without the context of other glycans and glycoconjugates. We used maps of g...

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    pub_type: 杂志文章


    authors: Narimatsu Y,Joshi HJ,Nason R,Van Coillie J,Karlsson R,Sun L,Ye Z,Chen YH,Schjoldager KT,Steentoft C,Furukawa S,Bensing BA,Sullam PM,Thompson AJ,Paulson JC,Büll C,Adema GJ,Mandel U,Hansen L,Bennett EP,Varki A,Vak

    更新日期:2019-07-25 00:00:00

  • Tissue-specific splicing of disordered segments that embed binding motifs rewires protein interaction networks.

    abstract::Alternative inclusion of exons increases the functional diversity of proteins. Among alternatively spliced exons, tissue-specific exons play a critical role in maintaining tissue identity. This raises the question of how tissue-specific protein-coding exons influence protein function. Here we investigate the structura...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Buljan M,Chalancon G,Eustermann S,Wagner GP,Fuxreiter M,Bateman A,Babu MM

    更新日期:2012-06-29 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


    authors: Kang R,Zelazowski MJ,Cole F

    更新日期:2018-03-01 00:00:00

  • Manipulation by Methylation: Garnishing mRNAs with m6Am.

    abstract::In two recent publications in Molecular Cell,Boulias et al. (2019) and Sendinc et al. (2019) use complementary approaches to map m6Am modification sites transcriptome-wide and demonstrate that m6Am can repress translation while increasing the stability of a subset of low-abundance transcripts. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Doxtader KA,Nam Y

    更新日期:2019-08-08 00:00:00