Rif1 Prevents Resection of DNA Breaks and Promotes Immunoglobulin Class Switching

被引：322

作者：

Di Virgilio, Michela ^{[1
]}

Callen, Elsa ^{[3
,4
]}

Yamane, Arito ^{[5
]}

Zhang, Wenzhu ^{[6
]}

Jankovic, Mila ^{[1
]}

Gitlin, Alexander D. ^{[1
]}

Feldhahn, Niklas ^{[1
]}

Resch, Wolfgang ^{[5
]}

Oliveira, Thiago Y. ^{[1
,7
,8
]}

Chait, Brian T. ^{[6
]}

Nussenzweig, Andre ^{[3
,4
]}

Casellas, Rafael ^{[5
]}

Robbiani, Davide F. ^{[1
]}

Nussenzweig, Michel C. ^{[1
,2
]}

机构：

[1] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA

[2] Rockefeller Univ, Howard Hughes Med Inst HHMI, New York, NY 10065 USA

[3] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA

[4] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[5] NCI, Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, NIH, Bethesda, MD 20892 USA

[6] Rockefeller Univ, Lab Mass Spectrometry & Gaseous Ion Chem, New York, NY 10065 USA

[7] Univ Sao Paulo, Fac Med, Dept Genet, BR-14049 Ribeirao Preto, Brazil

[8] Natl Inst Sci & Technol Stem Cells & Cell Therapy, BR-14049 Ribeirao Preto, Brazil

来源：

SCIENCE | 2013年 / 339卷 / 6120期

关键词：

53BP1; PROTEIN; REPAIR; DAMAGE; AID; RECOMBINATION; REGULATOR; TELOMERES; SITES; FOCUS;

D O I：

10.1126/science.1230624

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：

DNA double-strand breaks (DSBs) represent a threat to the genome because they can lead to the loss of genetic information and chromosome rearrangements. The DNA repair protein p53 binding protein 1 (53BP1) protects the genome by limiting nucleolytic processing of DSBs by a mechanism that requires its phosphorylation, but whether 53BP1 does so directly is not known. Here, we identify Rap1-interacting factor 1 (Rif1) as an ATM (ataxia-telangiectasia mutated) phosphorylation-dependent interactor of 53BP1 and show that absence of Rif1 results in 5'-3' DNA-end resection in mice. Consistent with enhanced DNA resection, Rif1 deficiency impairs DNA repair in the G(1) and S phases of the cell cycle, interferes with class switch recombination in B lymphocytes, and leads to accumulation of chromosome DSBs.

引用

页码：711 / 715

页数：5

共 26 条

[1] Tying the loose ends together in DNA double strand break repair with 53BP1 [J].