Regulation of the Fanconi anemia pathway by a SUMO-like delivery network

被引：90

作者：

Yang, Kailin ^{[1
,2
]}

Moldovan, George-Lucian ^{[1
]}

Vinciguerra, Patrizia ^{[1
]}

Murai, Junko ^{[3
]}

Takeda, Shunichi ^{[3
]}

D'Andrea, Alan D. ^{[1
]}

机构：

[1] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Leder Human Biol Program, Biol & Biomed Sci Program, Boston, MA 02115 USA

[3] Kyoto Univ, Dept Radiat Genet, Grad Sch Med, Sakyo Ku, Kyoto 6068501, Japan

来源：

GENES & DEVELOPMENT | 2011年 / 25卷 / 17期

基金：

瑞士国家科学基金会;

关键词：

Fanconi anemia; deubiquitinating enzymes; PCNA; SUMO-like domains; CROSS-LINK REPAIR; STRAND BREAK REPAIR; DNA-POLYMERASE-ETA; HOMOLOGOUS RECOMBINATION; DEUBIQUITINATING ENZYMES; MONOUBIQUITINATED PCNA; TRANSLESION SYNTHESIS; GENOMIC STABILITY; VERTEBRATE CELLS; UBIQUITIN;

D O I：

10.1101/gad.17020911

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The USP1/UAF1 complex deubiquitinates the Fanconi anemia protein FANCD2, thereby promoting homologous recombination and DNA cross-link repair. How USP1/UAF1 is targeted to the FANCD2/FANCI heterodimer has remained unknown. Here we show that UAF1 contains a tandem repeat of SUMO-like domains in its C terminus (SLD1 and SLD2). SLD2 binds directly to a SUMO-like domain-interacting motif (SIM) on FANCI. Deletion of the SLD2 sequence of UAF1 or mutation of the SIM on FANCI disrupts UAF1/FANCI binding and inhibits FANCD2 deubiquitination and DNA repair. The USP1/UAF1 complex also deubiquitinates PCNA-Ub, and deubiquitination requires the PCNA-binding protein hELG1. The SLD2 sequence of UAF1 binds to a SIM on hELG1, thus targeting the USP1/UAF1 complex to its PCNA-Ub substrate. We propose that the regulated targeting of USP1/UAF1 to its DNA repair substrates, FANCD2-Ub and PCNA-Ub, by SLD-SIM interactions coordinates homologous recombination and translesion DNA synthesis.

引用

页码：1847 / 1858

页数：12

共 51 条

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