ChAM, a novel motif that mediates PALB2 intrinsic chromatin binding and facilitates DNA repair

被引：43

作者：

Bleuyard, Jean-Yves ^{[1
]}

Buisson, Remi ^{[2
]}

Masson, Jean-Yves ^{[2
]}

Esashi, Fumiko ^{[1
]}

机构：

[1] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

[2] Univ Laval, Canc Res Ctr, Genome Stabil Lab, Hotel Dieu Quebec, Quebec City, PQ G1R 2J6, Canada

来源：

EMBO REPORTS | 2012年 / 13卷 / 02期

关键词：

PALB2; chromatin association; homologous recombination; DNA repair; cancer; HOMOLOGOUS RECOMBINATION; FANCONI-ANEMIA; CANCER; BRCA2; MUTATIONS; PARTNER; BREAKS; MRG15;

D O I：

10.1038/embor.2011.243

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The partner and localizer of breast cancer 2 susceptibility protein (PALB2) is crucial for the repair of DNA damage by homologous recombination. Here, we report that chromatin-association motif (ChAM), an evolutionarily conserved motif in PALB2, is necessary and sufficient to mediate its chromatin association in both unperturbed and damaged cells. ChAM is distinct from the previously described PALB2 DNA-binding regions. Deletion of ChAM decreases PALB2 and Rad51 accumulation at DNA damage sites and confers cellular hypersensitivity to the genotoxic drug mitomycin C. These results suggest that PALB2 chromatin association via ChAM facilitates PALB2 function in the cellular resistance to DNA damage.

引用

页码：135 / 141

页数：7

共 19 条

[1] Assembly and function of DNA double-strand break repair foci in mammalian cells [J].

Bekker-Jensen, Simon ;

Mailand, Niels .

DNA REPAIR, 2010, 9 (12) :1219-1228

[2] Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination [J].

Buisson, Remi ;

Dion-Cote, Anne-Marie ;

Coulombe, Yan ;

Launay, Helene ;

Cai, Hong ;

Stasiak, Alicja Z. ;

Stasiak, Andrzej ;

Xia, Bing ;

Masson, Jean-Yves .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2010, 17 (10) :1247-+

[3] Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2 [J].

Dray, Eloiese ;

Etchin, Julia ;

Wiese, Claudia ;

Saro, Dorina ;

Williams, Gareth J. ;

Hammel, Michal ;

Yu, Xiong ;

Galkin, Vitold E. ;

Liu, Dongqing ;

Tsai, Miaw-Sheue ;

Sy, Shirley M-H ;

Schild, David ;

Egelman, Edward ;

Chen, Junjie ;

Sung, Patrick .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2010, 17 (10) :1255-+

[4] A recurrent mutation in PALB2 in Finnish cancer families [J].

Erkko, Hannele ;

Xia, Bing ;

Nikkilae, Jenni ;

Schleutker, Johanna ;

Syrjaekoski, Kirsi ;

Mannermaa, Arto ;

Kallioniemi, Anne ;

Pylkas, Katri ;

Karppinen, Sanna-Maria ;

Rapakko, Katrin ;

Miron, Alexander ;

Sheng, Qing ;

Li, Guilan ;

Mattila, Henna ;

Bell, Daphne W. ;

Haber, Daniel A. ;

Grip, Mervi ;

Reiman, Mervi ;

Jukkola-Vuorinen, Arja ;

Mustonen, Aki ;

Kere, Juha ;

Aaltonen, Lauri A. ;

Kosma, Veli-Matti ;

Kataja, Vesa ;

Soini, Ylermi ;

Drapkin, Ronny I. ;

Livingston, David M. ;

Winqvist, Robert .

NATURE, 2007, 446 (7133) :316-319

[5] Recognizing and remodeling the nucleosome [J].

Glatt, Sebastian ;

Alfieri, Claudio ;

Mueller, Christoph W. .

CURRENT OPINION IN STRUCTURAL BIOLOGY, 2011, 21 (03) :335-341

[6] MRG15 binds directly to PALB2 and stimulates homology-directed repair of chromosomal breaks [J].

Hayakawa, Tomohiro ;

Zhang, Fan ;

Hayakawa, Noriyo ;

Ohtani, Yasuko ;

Shinmyozu, Kaori ;

Nakayama, Jun-ichi ;

Andreassen, Paul R. .

JOURNAL OF CELL SCIENCE, 2010, 123 (07) :1124-1130

[7] Coping with DNA double strand breaks [J].

Hiom, Kevin .

DNA REPAIR, 2010, 9 (12) :1256-1263

[8] The DNA-damage response in human biology and disease [J].

Jackson, Stephen P. ;

Bartek, Jiri .

NATURE, 2009, 461 (7267) :1071-1078

[9] PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene [J].

Rahman, Nazneen ;

Seal, Sheila ;

Thompson, Deborah ;

Kelly, Patrick ;

Renwick, Anthony ;

Elliott, Anna ;

Reid, Sarah ;

Spanova, Katarina ;

Barfoot, Rita ;

Chagtai, Tasnim ;

Jayatilake, Hiran ;

McGuffog, Lesley ;

Hanks, Sandra ;

Evans, D. Gareth ;

Eccles, Diana ;

Easton, Douglas F. ;

Stratton, Michael R. .

NATURE GENETICS, 2007, 39 (02) :165-167

[10] Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer [J].

Reid, Sarah ;

Schindler, Detlev ;

Hanenberg, Helmut ;

Barker, Karen ;

Hanks, Sandra ;

Kalb, Reinhard ;

Neveling, Kornelia ;

Kelly, Patrick ;

Seal, Sheila ;

Freund, Marcel ;

Wurm, Melanie ;

Batish, Sat Dev ;

Lach, Francis P. ;

Yetgin, Sevgi ;

Neitzel, Heidemarie ;

Ariffin, Hany ;

Tischkowitz, Marc ;

Mathew, Christopher G. ;

D Auerbach, Arleen ;

Rahman, Nazneen .

NATURE GENETICS, 2007, 39 (02) :162-164

← 1 2 →