000174544 001__ 174544
000174544 005__ 20181203022623.0
000174544 0247_ $$2doi$$a10.1158/1541-7786.MCR-11-0134
000174544 022__ $$a1557-3125
000174544 02470 $$2ISI$$a000301777700013
000174544 037__ $$aARTICLE
000174544 245__ $$aThe ATM substrate KAP1 controls DNA repair in heterochromatin: Regulation by HP1 proteins and Serine 473/824 phosphorylation
000174544 260__ $$c2012
000174544 269__ $$a2012
000174544 336__ $$aJournal Articles
000174544 520__ $$aThe repair of DNA damage in highly compact, transcriptionally silent heterochromatin requires that repair and chromatin packaging machineries be tightly coupled and regulated. KAP1 is a heterochromatin protein and co-repressor which binds to HP1 during gene silencing, but is also robustly phosphorylated by ATM at serine 824 in response to DNA damage. The interplay between HP1-KAP1 binding/ATM phosphorylation during DNA repair is not known. We show that HP1α and unmodified KAP1 are enriched in endogenous heterochromatic loci and at a silent transgene prior to damage. Following damage, γH2AX and pKAP1-s824 rapidly increase and persist at these loci. Cells which lack HP1 fail to form discreet pKAP1-s824 foci after damage but levels are higher and more persistent. KAP1 is phosphorylated at Serine 473 in response to DNA damage and its levels are also modulated by HP1. Unlike pKAP1-s824, pKAP1-s473 does not accumulate at damage foci but is diffusely localized in the nucleus. While HP1 association tempers KAP1 phosphorylation, this interaction also slows the resolution of γH2AX foci. Thus, HP1-dependent regulation of KAP1 influences DNA repair in heterochromatin.
000174544 6531_ $$aDouble-Strand Breaks
000174544 6531_ $$aZinc-Finger Proteins
000174544 6531_ $$aHistone H2Ax
000174544 6531_ $$aMammalian-Cells
000174544 6531_ $$aChromatin
000174544 6531_ $$aCorepressor
000174544 6531_ $$aDamage
000174544 6531_ $$aComplexes
000174544 6531_ $$aChromosomes
000174544 6531_ $$aColocalizes
000174544 700__ $$aWhite, David
000174544 700__ $$aRafalska-Metcalf, Ilona U.
000174544 700__ $$aIvanov, Alexey V.
000174544 700__ $$0242332$$aCorsinotti, Andrea$$g177011
000174544 700__ $$aPeng, Hongzhuang
000174544 700__ $$aLee, Sheng-Chung
000174544 700__ $$0240083$$aTrono, Didier$$g167919
000174544 700__ $$aJanicki, Susan M.
000174544 700__ $$aRauscher, Frank J.
000174544 773__ $$j1$$q3-10$$tMolecular cancer research : MCR
000174544 909C0 $$0252036$$pLVG$$xU11172
000174544 909CO $$ooai:infoscience.tind.io:174544$$pSV$$particle
000174544 917Z8 $$x169414
000174544 917Z8 $$x148230
000174544 937__ $$aEPFL-ARTICLE-174544
000174544 973__ $$aOTHER$$rNON-REVIEWED$$sPUBLISHED
000174544 980__ $$aARTICLE