PARP3 is a sensor of nicked nucleosomes and monoribosylates histone H2BGlu2

被引:69
作者
Grundy, Gabrielle J. [1 ]
Polo, Luis M. [2 ]
Zeng, Zhihong [1 ]
Rulten, Stuart L. [1 ]
Hoch, Nicolas C. [1 ,3 ]
Paomephan, Pathompong [1 ]
Xu, Yingqi [4 ]
Sweet, Steve M. [1 ]
Thorne, Alan W. [5 ]
Oliver, Antony W. [2 ]
Matthews, Steve J. [4 ]
Pearl, Laurence H. [2 ]
Caldecott, Keith W. [1 ]
机构
[1] Univ Sussex, Sch Life Sci, Genome Damage & Stabil Ctr, Sci Pk Rd, Brighton BN1 9RQ, E Sussex, England
[2] Univ Sussex, Sch Life Sci, Genome Damage & Stabil Ctr, Canc Res UK DNA Repair Enzymes Grp, Sci Pk Rd, Brighton BN1 9RQ, E Sussex, England
[3] Minist Educ Brazil, CAPES Fdn, BR-70040020 Brasilia, DF, Brazil
[4] Imperial Coll London, Fac Nat Sci, Dept Life Sci, Cross Fac,NMR Ctr, London SW7 2AZ, England
[5] Univ Portsmouth, Inst Biomed & Biomol Sci, St Michaels Bldg, Portsmouth PO1 2DT, Hants, England
基金
英国惠康基金;
关键词
STRAND BREAK REPAIR; END-JOINING PATHWAYS; ADP-RIBOSYLATION; POLY(ADP-RIBOSE) POLYMERASE; DNA-DAMAGE; HOMOLOGOUS RECOMBINATION; CELLULAR-RESPONSE; NUCLEAR PROTEINS; CELLS; XRCC1;
D O I
10.1038/ncomms12404
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
PARP3 is a member of the ADP-ribosyl transferase superfamily that we show accelerates the repair of chromosomal DNA single-strand breaks in avian DT40 cells. Two-dimensional nuclear magnetic resonance experiments reveal that PARP3 employs a conserved DNA-binding interface to detect and stably bind DNA breaks and to accumulate at sites of chromosome damage. PARP3 preferentially binds to and is activated by mononucleosomes containing nicked DNA and which target PARP3 trans-ribosylation activity to a single-histone substrate. Although nicks in naked DNA stimulate PARP3 autoribosylation, nicks in mononucleosomes promote the trans-ribosylation of histone H2B specifically at Glu2. These data identify PARP3 as a molecular sensor of nicked nucleosomes and demonstrate, for the first time, the ribosylation of chromatin at a site-specific DNA single-strand break.
引用
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页数:12
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