Abstract
▪ Abstract DNA checkpoints play a significant role in cancer pathology, perhaps most notably in maintaining genome stability. This review summarizes the genetic and molecular mechanisms of checkpoint activation in response to DNA damage. The major checkpoint proteins common to all eukaryotes are identified and discussed, together with how the checkpoint proteins interact to induce arrest within each cell cycle phase. Also discussed are the molecular signals that activate checkpoint responses, including single-strand DNA, double-strand breaks, and aberrant replication forks. We address the connection between checkpoint proteins and damage repair mechanisms, how cells recover from an arrest response, and additional roles that checkpoint proteins play in DNA metabolism. Finally, the connection between checkpoint gene mutation and genomic instability is considered.
References
239
Referenced
595
10.1074/jbc.274.26.18808
10.1101/gad.914401
10.1038/35003120
10.1091/mbc.5.2.147
10.1038/ncb1101-958
10.1038/35050642
10.1074/jbc.M106460200
10.1073/pnas.92.25.11791
10.1091/mbc.11.1.1
10.1126/science.281.5383.1674
10.1097/00001622-200201000-00015
10.1016/S0955-0674(00)00280-5
10.1128/MCB.20.12.4393-4404.2000
10.1126/science.286.5449.2528
10.1074/jbc.C000276200
10.1128/MCB.20.23.8758-8766.2000
10.1128/MCB.19.11.7681
10.1101/gad.14.4.397
/ Genes Dev. by Brown EJ (2000)10.1093/nar/28.19.3725
10.1073/pnas.93.26.15075
10.1016/S0959-437X(01)00270-2
10.1038/35075107
10.1074/jbc.M102946200
10.1128/MCB.21.15.5214-5222.2001
10.1126/science.281.5383.1677
10.1016/S0092-8674(00)81175-7
10.1126/science.287.5459.1765
10.1128/MCB.20.4.1254-1262.2000
10.1101/gad.221402
10.1074/jbc.274.51.36679
10.1128/MCB.21.21.7150-7162.2001
10.1093/nar/27.10.2072
10.1038/44188
10.1101/gad.14.3.278
/ Genes Dev. by Chehab NH (2000)10.1128/MCB.18.12.7360
10.1093/emboj/20.22.6485
10.1038/5991
10.1126/science.1065521
10.1126/science.286.5442.1162
10.1016/S1097-2765(00)00063-0
10.1038/35003501
10.1128/MCB.20.7.2378-2384.2000
10.1074/jbc.M103414200
10.1038/nrm805
10.1128/MCB.18.5.2721
10.1016/S0960-9822(00)00447-4
10.1016/S0014-5793(00)02198-0
10.1101/gad.12.18.2956
10.1101/gad.8.21.2540
10.1128/MCB.16.9.4832
10.1093/emboj/18.24.7002
10.1074/jbc.M105735200
10.1016/S0009-2797(01)00211-3
10.1038/15623
10.1016/S0955-0674(00)00151-4
10.1016/S1097-2765(00)80128-8
10.1101/gad.6.11.2035
10.1016/S1097-2765(00)80364-0
10.1038/35071124
10.1128/MCB.18.3.1190
10.1242/jcs.115.8.1749
/ J. Cell Sci. by Fitz Gerald JN (2002)10.1016/S0027-5107(00)00049-X
10.1038/sj.onc.1204574
10.1093/genetics/157.2.567
/ Genetics by Foss EJ (2001)10.1242/jcs.113.15.2641
/ J. Cell Sci. by Frei C (2000)10.1101/gad.14.1.81
/ Genes Dev. by Frei C (2000)10.1093/emboj/18.11.3173
10.1016/S1097-2765(00)80438-4
10.1128/MCB.15.11.6128
10.1091/mbc.12.10.2987
{'key': 'b71', 'first-page': '3299', 'volume': '60', 'author': 'Gatei M', 'year': '2000', 'journal-title': 'Cancer Res.'}
/ Cancer Res. by Gatei M (2000)10.1091/mbc.9.9.2361
10.1023/A:1018779830743
10.1038/sj.cdd.4400663
{'key': 'b75', 'first-page': '149', 'volume': '11', 'author': 'Geyer RK', 'year': '2000', 'journal-title': 'Cell Growth Differ.'}
/ Cell Growth Differ. by Geyer RK (2000)10.1016/S1097-2765(01)00267-2
10.1126/science.281.5379.1009
10.1038/sj.onc.1204259
10.1016/S0960-9822(99)00263-8
10.1007/s004380050925
10.1002/j.1460-2075.1995.tb00269.x
10.1093/genetics/153.2.607
/ Genetics by Grushcow JM (1999)10.1101/gad.842500
10.1006/geno.2000.6142
10.1016/0092-8674(93)90499-G
10.1126/science.2683079
10.1038/387296a0
10.1016/S0960-9822(00)00855-1
10.1016/S1097-2765(00)80002-7
10.1126/science.287.5459.1824
10.1101/gad.938102
10.1016/S0921-8777(00)00034-3
10.1080/10409239991209255
10.1083/jcb.141.4.875
{'key': 'b95', 'first-page': '2464', 'volume': '59', 'author': 'Kamijo T', 'year': '1999', 'journal-title': 'Cancer Res.'}
/ Cancer Res. by Kamijo T (1999)10.1083/jcb.200108016
10.1038/35043058
{'key': 'b98', 'first-page': '6304', 'volume': '51', 'author': 'Kastan MB', 'year': '1991', 'journal-title': 'Cancer Res.'}
/ Cancer Res. by Kastan MB (1991)10.1038/sj.onc.1205229
10.1038/85798
10.1073/pnas.96.26.14973
10.1128/MCB.21.11.3725-3737.2001
10.1093/genetics/159.4.1501
/ Genetics by Klein HL (2001)10.1016/0165-4608(82)90085-1
10.1038/71316
10.1126/science.1063827
10.1146/annurev.immunol.15.1.177
10.1091/mbc.12.3.551
10.1038/35004614
10.1016/S1097-2765(00)80390-1
10.1038/35018134
10.1038/35007091
10.1101/gad.12.3.382
10.1073/pnas.201373498
10.1128/MCB.19.7.5113
{'key': 'b116', 'first-page': '3075', 'volume': '51', 'author': 'Loeb LA', 'year': '1991', 'journal-title': 'Cancer Res.'}
/ Cancer Res. by Loeb LA (1991)10.1093/nar/24.18.3533
10.1093/genetics/155.4.1577
/ Genetics by Longhese MP (2000)10.1038/35087613
10.1016/S0960-9822(00)00026-9
10.1038/383840a0
10.1126/science.270.5241.1488
10.1126/science.288.5470.1425
10.1074/jbc.M102245200
10.1126/science.1978757
10.1093/emboj/16.3.639
10.1093/emboj/17.24.7239
10.1128/MCB.17.10.6087
10.1126/science.282.5395.1893
10.1093/genetics/152.4.1501
/ Genetics by Matsuura A (1999)10.1016/S0960-9822(99)80424-2
10.1101/gad.903501
/ Genes Dev. by Melo JA (2001)10.1016/S0092-8674(00)80772-2
10.1093/emboj/19.3.463
10.1016/S1097-2765(00)80202-6
10.1073/pnas.062702199
10.1128/MCB.20.16.5888-5896.2000
10.1101/gad.10.20.2632
10.1016/S0960-9822(02)00739-X
10.1128/MCB.18.8.4914
10.1091/mbc.12.5.1199
10.1038/ncb741
10.1101/gad.14.16.2046
/ Genes Dev. by Paciotti V (2000)10.1128/MCB.21.12.3913-3925.2001
10.1073/pnas.77.12.7315
10.1038/sj.onc.1205060
10.1074/jbc.273.29.18332
10.1073/pnas.111125998
10.1093/genetics/150.1.75
/ Genetics by Paulovich AG (1998)10.1016/0092-8674(95)90481-6
10.1016/S1097-2765(01)00177-0
10.1126/science.277.5331.1501
10.1126/science.294.5540.115
10.1101/gad.949802
10.1128/MCB.21.5.1499-1508.2001
10.1128/MCB.19.9.6065
10.1038/sj.onc.1203124
10.1093/emboj/19.21.5801
10.1016/S1097-2765(02)00507-5
10.1101/gad.11.24.3387
10.1126/science.286.5442.1166
10.1126/science.277.5331.1497
10.1016/0092-8674(93)90493-A
10.1038/27001
10.1006/jmbi.1995.0641
10.1126/science.7792600
10.1101/gad.193901
10.1038/35019108
10.1016/S0092-8674(00)81847-4
10.1101/gad.13.12.1501
10.1101/gad.14.3.289
/ Genes Dev. by Shieh SY (2000)10.1146/annurev.genet.31.1.635
10.1016/S0959-437X(00)00159-3
10.1091/mbc.10.12.3991
10.1101/gad.11.22.3032
10.1093/genetics/138.2.271
/ Genetics by Siede W (1994)10.1073/pnas.96.20.11134
10.1101/gad.13.8.916
10.1038/35023629
10.1038/sj.onc.1203334
10.1126/science.1074023
10.1091/mbc.10.6.1985
10.1016/S0092-8674(00)81547-0
10.1128/MCB.12.2.563
10.1093/emboj/19.23.6517
10.1038/35003506
10.1038/ncb1101-966
10.1091/mbc.10.11.3607
10.1038/sj.onc.1204252
10.1038/376358a0
10.1038/35087607
10.1093/genetics/153.2.621
/ Genetics by Thompson DA (1999)10.1101/gad.851000
10.1101/gad.13.15.1936
10.1093/emboj/17.10.2728
10.1016/S0021-9258(18)52386-3
/ J. Biol. Chem. by Tsurimoto T (1991)10.1073/pnas.93.13.6236
10.1016/S1097-2765(01)00270-2
10.1016/S1097-2765(01)00216-7
10.1074/jbc.M101831200
10.1093/nar/28.13.2481
10.1007/s004380050913
10.1093/emboj/17.19.5679
10.1074/jbc.274.2.567
10.1128/MCB.21.3.755-764.2001
10.1126/science.271.5247.353
10.1073/pnas.96.7.3824
10.1093/genetics/160.4.1295
/ Genetics by Wang H (2002){'key': 'b209', 'first-page': '8554', 'volume': '61', 'author': 'Wang H', 'year': '2001', 'journal-title': 'Cancer Res.'}
/ Cancer Res. by Wang H (2001){'key': 'b210', 'first-page': '270', 'volume': '61', 'author': 'Wang H', 'year': '2001', 'journal-title': 'Cancer Res.'}
/ Cancer Res. by Wang H (2001)10.1101/gad.14.8.927
/ Genes Dev. by Wang Y (2000)10.1074/jbc.M009785200
10.2307/3583517
10.1016/S0959-437X(98)80140-8
10.1126/science.3291120
10.1128/MCB.10.12.6554
10.1101/gad.8.6.652
10.1093/emboj/18.19.5334
10.1093/nar/25.11.2138
10.1091/mbc.01-03-0104
10.1073/pnas.95.13.7445
10.1074/jbc.M106050200
10.1016/0092-8674(92)90518-H
10.1128/MCB.21.10.3445-3450.2001
10.1101/gad.10.19.2401
10.1128/MCB.22.2.555-566.2002
{'key': 'b227', 'first-page': '2316', 'volume': '58', 'author': 'Yamazaki V', 'year': '1998', 'journal-title': 'Cancer Res.'}
/ Cancer Res. by Yamazaki V (1998)10.1083/jcb.136.2.345
10.1073/pnas.96.9.4983
10.1038/ng837
10.1074/jbc.M204120200
10.1038/35013083
10.1093/emboj/20.13.3544
10.1016/S1097-2765(00)80277-4
10.1073/pnas.062502299
10.1126/science.285.5428.747
10.1074/jbc.275.14.10342
10.1038/77139
10.1101/gad.950302
Dates
Type | When |
---|---|
Created | 22 years, 9 months ago (Nov. 12, 2002, 1:29 p.m.) |
Deposited | 2 years, 4 months ago (April 25, 2023, 8:22 a.m.) |
Indexed | 1 day, 5 hours ago (Aug. 29, 2025, 5:48 a.m.) |
Issued | 22 years, 8 months ago (Dec. 1, 2002) |
Published | 22 years, 8 months ago (Dec. 1, 2002) |
Published Print | 22 years, 8 months ago (Dec. 1, 2002) |
@article{Nyberg_2002, title={Toward Maintaining the Genome: DNA Damage and Replication Checkpoints}, volume={36}, ISSN={1545-2948}, url={http://dx.doi.org/10.1146/annurev.genet.36.060402.113540}, DOI={10.1146/annurev.genet.36.060402.113540}, number={1}, journal={Annual Review of Genetics}, publisher={Annual Reviews}, author={Nyberg, Kara A. and Michelson, Rhett J. and Putnam, Charles W. and Weinert, Ted A.}, year={2002}, month=dec, pages={617–656} }