Removal of shelterin reveals the telomere end-protection problem.
Removal of shelterin reveals the telomere end-protection problem.
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DOI:
10.1126/science.1218498
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发表时间:
2012-05-04
期刊:
影响因子:
--
通讯作者:
de Lange T
中科院分区:
文献类型:
--
作者:
Sfeir A;de Lange T
The telomere end-protection problem is defined by the aggregate of DNA damage signaling and repair pathways that require repression at telomeres. To define the end-protection problem, we removed the whole shelterin complex from mouse telomeres through conditional deletion of TRF1 and TRF2 in nonhomologous end-joining (NHEJ) deficient cells. The data reveal two DNA damage response pathways not previously observed upon deletion of individual shelterin proteins. The shelterin-free telomeres are processed by microhomology-mediated alternative-NHEJ when Ku70/80 is absent and are attacked by nucleolytic degradation in the absence of 53BP1. The data establish that the end-protection problem is specified by six pathways [ATM (ataxia telangiectasia mutated) and ATR (ataxia telangiectasia and Rad3 related) signaling, classical-NHEJ, alt-NHEJ, homologous recombination, and resection] and show how shelterin acts with general DNA damage response factors to solve this problem.
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影响因子:
64.5
作者:
Sfeir A;Kosiyatrakul ST;Hockemeyer D;MacRae SL;Karlseder J;Schildkraut CL;de Lange T
通讯作者:
de Lange T
DOI:
10.1126/science.1170633
发表时间:
2009-11-13
期刊:
Science (New York, N.Y.)
影响因子:
--
作者:
de Lange T
通讯作者:
de Lange T
影响因子:
4.5
作者:
Simsek D;Brunet E;Wong SY;Katyal S;Gao Y;McKinnon PJ;Lou J;Zhang L;Li J;Rebar EJ;Gregory PD;Holmes MC;Jasin M
通讯作者:
Jasin M
影响因子:
64.8
作者:
Yan, Catherine T.;Boboila, Cristian;Alt, Frederick W.
通讯作者:
Alt, Frederick W.
影响因子:
11.4
作者:
Rai, Rekha;Zheng, Hong;Chang, Sandy
通讯作者:
Chang, Sandy