Heterozygous mutations in PALB2 cause DNA replication and damage response defects

Nature Communications

Volumn 4, Issue , 2013, Pages

  Nikkilä, Jenni ^a,f   Parplys, Ann Christin ^b   Pylkäs, Katri ^a   Bose, Muthiah ^a   Huo, Yanying ^c   Borgmann, Kerstin ^b   Rapakko, Katrin ^d   Nieminen, Pentti ^a   Xia, Bing ^c   Pospiech, Helmut ^a,e   Winqvist, Robert ^a  

^a UNIVERSITY OF OULU   (Finland)

^b UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^c ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

^d OULU UNIVERSITY HOSPITAL   (Finland)

^e FRITZ LIPMANN INSTITUTE   (Germany)

^f INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ATR PROTEIN; CHECKPOINT KINASE 1; CHECKPOINT KINASE 2; CYCLIN DEPENDENT KINASE; ETOPOSIDE; PALB2 PROTEIN; PROTEIN; RAD51 PROTEIN; ROSCOVITINE; THREONINE; UNCLASSIFIED DRUG; ATM PROTEIN; ATR PROTEIN, HUMAN; BRCA1 PROTEIN; BRCA1 PROTEIN, HUMAN; BRCA2 PROTEIN; BRCA2 PROTEIN, HUMAN; CHEK2 PROTEIN, HUMAN; NUCLEAR PROTEIN; PALB2 PROTEIN, HUMAN; PROTEIN KINASE; TUMOR SUPPRESSOR PROTEIN;

AGED; ARTICLE; BREAST CANCER; CANCER SUSCEPTIBILITY; CHROMOSOMAL INSTABILITY; CLINICAL ARTICLE; CONTROLLED STUDY; DISEASE PREDISPOSITION; DNA DAMAGE; DNA REPLICATION; FAMILIAL CANCER; FEMALE; GENE MUTATION; GENOME ANALYSIS; GENOMIC INSTABILITY; HAPLOINSUFFICIENCY; HETEROZYGOTE; HOMOLOGOUS RECOMBINATION; HUMAN; HUMAN CELL; LYMPHOBLASTOID CELL LINE; LYMPHOCYTE; PERIPHERAL LYMPHOCYTE; PROTEIN ANALYSIS; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; BREAST TUMOR; CASE CONTROL STUDY; GENE EXPRESSION REGULATION; GENETIC PREDISPOSITION; GENETICS; METABOLISM; MUTATION; PATHOLOGY; PRIMARY CELL CULTURE; TUMOR CELL LINE;

ATAXIA TELANGIECTASIA MUTATED PROTEINS; BRCA1 PROTEIN; BRCA2 PROTEIN; BREAST NEOPLASMS; CASE-CONTROL STUDIES; CELL LINE, TUMOR; CHECKPOINT KINASE 2; CHROMOSOMAL INSTABILITY; DNA DAMAGE; DNA REPLICATION; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; GENETIC PREDISPOSITION TO DISEASE; HAPLOINSUFFICIENCY; HETEROZYGOTE; HUMANS; LYMPHOCYTES; MUTATION; NUCLEAR PROTEINS; PRIMARY CELL CULTURE; PROTEIN KINASES; TUMOR SUPPRESSOR PROTEINS;

EID: 84898615020     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms3578     Document Type: Article

References (40)

1. Xia, B. et al. Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol. Cell 22, 719-729 (2006).
2. Zhang, F. et al. PALB2 links BRCA1 and BRCA2 in the DNA-damage response. Curr. Biol. 19, 524-529 (2009).
3. Dray, E. et al. Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2. Nat. Struct. Mol. Biol. 17, 1255-1259 (2010).
4. Tischkowitz, M. & Xia, B. PALB2/FANCN-recombining cancer and Fanconi anemia. Cancer Res. 70, 7353-7359 (2010).
5. Xia, B. et al. Fanconi anemia is associated with a defect in the BRCA2 partner PALB2. Nat. Genet. 39, 159-161 (2007).
6. Erkko, H. et al. A recurrent mutation in PALB2 in Finnish cancer families. Nature 446, 316-319 (2007).
7. Rahman, N. et al. PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat. Genet. 39, 165-167 (2007).
8. Southey, M. C. et al. A PALB2 mutation associated with high risk of breast cancer. Breast Cancer Res. 12, R109 (2010).
9. Erkko, H. et al. Penetrance analysis of the PALB2 c.1592delT founder mutation. Clin. Cancer Res. 14, 4667-4671 (2008).
10. Reid, S. et al. Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nat. Genet. 39, 162-164 (2007).
11. Hellebrand, H. et al. Germline mutations in the PALB2 gene are population specific and occur with low frequencies in familial breast cancer. Hum. Mutat. 32, E2176-E2188 (2011).
12. Casadei, S. et al. Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Cancer Res. 71, 2222-2229 (2011).
13. Tischkowitz, M. et al. Rare germline mutations in PALB2 and breast cancer risk: a population-based study. Hum. Mutat. 33, 674-680 (2012).
14. Bryant, H. E. et al. PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination. EMBO J. 28, 2601-2615 (2009).
15. Schwab, R. A. et al. ATR activation and replication fork restart are defective in FANCM-deficient cells. EMBO J. 29, 806-818 (2010).
16. Daboussi, F. et al. A homologous recombination defect affects replication-fork progression in mammalian cells. J. Cell Sci. 121, 162-166 (2008).
17. Karnani, N. & Dutta, A. The effect of the intra-S-phase checkpoint on origins of replication in human cells. Genes Dev. 25, 621-633 (2011).
18. Liu, Q. et al. Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev. 14, 1448-1459 (2000).
19. Zhao, H. & Piwnica-Worms, H. ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Mol. Cell Biol. 21, 4129-4139 (2001).
20. Ge, X. Q. & Blow, J. J. Chk1 inhibits replication factory activation but allows dormant origin firing in existing factories. J. Cell Biol. 191, 1285-1297 (2010).
21. Syljuasen, R. G. et al. Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage. Mol. Cell. Biol 25, 3553-3562 (2005).
22. Petermann, E. & Caldecott, K. W. Evidence that the ATR/Chk1 pathway maintains normal replication fork progression during unperturbed S phase. Cell Cycle 5, 2203-2209 (2006).
23. Maya-Mendoza, A., Petermann, E., Gillespie, D. A., Caldecott, K. W. & Jackson, D. A. Chk1 regulates the density of active replication origins during the vertebrate S phase. EMBO J. 26, 2719-2731 (2007).
24. Petermann, E., Woodcock, M. & Helleday, T. Chk1 promotes replication fork progression by controlling replication initiation. Proc. Natl Acad. Sci. USA 107, 16090-16095 (2010).
25. Araki, H. Cyclin-dependent kinase-dependent initiation of chromosomal DNA replication. Curr. Opin. Cell Biol. 22, 766-771 (2010).
26. Beck, H. et al. Cyclin-dependent kinase suppression by WEE1 kinase protects the genome through control of replication initiation and nucleotide consumption. Mol. Cell Biol. 32, 4226-4236 (2012).
27. Gilad, O. et al. Combining ATR suppression with oncogenic Ras synergistically increases genomic instability, causing synthetic lethality or tumorigenesis in a dosage-dependent manner. Cancer Res. 70, 9693-9702 (2010).
28. Brown, E. J. & Baltimore, D. Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance. Genes Dev. 17, 615-628 (2003).
29. Menzel, T. et al. A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance. EMBO Rep. 12, 705-712 (2011).
30. Theunissen, J. W. & Petrini, J. H. Methods for studying the cellular response to DNA damage: influence of the Mre11 complex on chromosome metabolism. Methods Enzymol. 409, 251-284 (2006).
31. Reinhardt, H. C. & Yaffe, M. B. Kinases that control the cell cycle in response to DNA damage: Chk1, Chk2, and MK2. Curr. Opin. Cell Biol. 21, 245-255 (2009).
32. Soni, V., Cahir-McFarland, E. & Kieff, E. LMP1 TRAFficking activates growth and survival pathways. Adv. Exp. Med. Biol. 597, 173-187 (2007).
33. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646-674 (2011).
34. Halazonetis, T. D., Gorgoulis, V. G. & Bartek, J. An oncogene-induced DNA damage model for cancer development. Science 319, 1352-1355 (2008).
35. Gorgoulis, V. G. et al. Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 434, 907-913 (2005).
36. Konishi, H. et al. Mutation of a single allele of the cancer susceptibility gene BRCA1 leads to genomic instability in human breast epithelial cells. Proc. Natl Acad. Sci. USA 108, 17773-17778 (2011).
37. Heikkinen, K. et al. RAD50 and NBS1 are breast cancer susceptibility genes associated with genomic instability. Carcinogenesis 27, 1593-1599 (2006).
38. Verma, R. S. & Babu, A. (ed.) Human chromosomes, manual of basic techniques (Pergamon Press, Inc, 1989).
39. Parplys, A. C., Petermann, E., Petersen, C., Dikomey, E. & Borgmann, K. DNA damage by X-rays and their impact on replication processes. Radiother. Oncol. 102, 466-471 (2012).
40. Jackson, D. A. & Pombo, A. Replicon clusters are stable units of chromosome structure: evidence that nuclear organization contributes to the efficient activation and propagation of S phase in human cells. J. Cell Biol. 140, 1285-1295 (1998).