title: Chromatin remodeling, DNA damage repair and aging.
abstract: Cells are constantly exposed to a variety of environmental and endogenous conditions causing DNA damage, which is detected and repaired by conserved DNA repair pathways to maintain genomic integrity. Chromatin remodeling is critical in this process, as the organization of eukaryotic DNA into compact chromatin presents a natural barrier to all DNA-related events. Studies on human premature aging syndromes together with normal aging have suggested that accumulated damages might lead to exhaustion of resources that are required for physiological functions and thus accelerate aging. In this manuscript, combining the present understandings and latest findings, we focus mainly on discussing the role of chromatin remodeling in the repair of DNA double-strand breaks (DSBs) and regulation of aging.
authors: Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, China ; Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors: Baohua
authors: B
authors: Liu
authors: Raymond Kh
authors: RKh
authors: Yip
authors: Zhongjun
authors: Z
authors: Zhou
keywords: Aging; DNA double strand break repair.; Epigenetics; Histone modifications; Longevity; Sirtuins
references: Genes Dev. 2005 Jul 15;19(14):1656-61
references: 16024655
references: Nature. 2007 May 10;447(7141):178-82
references: 17468743
references: Mol Cell Biol. 2005 Jun;25(12):4903-13
references: 15923609
references: Nature. 2012 Feb 22;483(7388):218-21
references: 22367546
references: Cell. 2007 Feb 23;128(4):693-705
references: 17320507
references: Nature. 2005 Jul 14;436(7048):294-8
references: 16015338
references: J Biol Chem. 2001 May 11;276(19):16439-46
references: 11279038
references: Curr Opin Genet Dev. 2007 Apr;17(2):126-31
references: 17320375
references: Nat Immunol. 2003 Feb;4(2):124-31
references: 12496962
references: J Med Genet. 2004 May;41(5):e67
references: 15121795
references: J Cell Sci. 2006 Jul 1;119(Pt 13):2704-14
references: 16772334
references: J Cell Sci. 2007 Mar 1;120(Pt 5):713-21
references: 17314245
references: Nat Genet. 1999 Sep;23(1):62-6
references: 10471500
references: Exp Gerontol. 1996 Jan-Apr;31(1-2):281-93
references: 8706797
references: Mol Cell. 2004 Jun 4;14(5):667-73
references: 15175161
references: Mol Cell. 2010 May 28;38(4):590-602
references: 20513433
references: Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7376-81
references: 10377422
references: Oncogene. 2004 Jan 8;23(1):149-56
references: 14712220
references: Nat Immunol. 2004 May;5(5):481-7
references: 15077110
references: J Biol Chem. 1999 Dec 31;274(53):37795-9
references: 10608841
references: Cell. 1998 Dec 23;95(7):891-902
references: 9875844
references: Nat Cell Biol. 2008 Apr;10(4):452-9
references: 18311132
references: Science. 1993 Apr 9;260(5105):207-10
references: 8469973
references: PLoS One. 2008 Mar 05;3(3):e1710
references: 18320031
references: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15706-11
references: 14668445
references: Mol Cell Biol. 2000 Mar;20(6):1899-910
references: 10688638
references: Nucleic Acids Res. 2009 Apr;37(5):1363-77
references: 19139074
references: Mol Cell. 2008 Jul 25;31(2):167-77
references: 18657500
references: Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1584-9
references: 15668383
references: Nature. 2003 Sep 11;425(6954):191-6
references: 12939617
references: Mol Cell. 2000 Nov;6(5):989-98
references: 11106739
references: Cell. 2004 Dec 17;119(6):767-75
references: 15607974
references: Genetics. 1979 Sep;93(1):37-50
references: 17248968
references: Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8703-8
references: 16738054
references: J Radiat Res. 2008 Sep;49(5):451-64
references: 18772547
references: Mol Cell Biol. 2005 Jun;25(12):5292-305
references: 15923642
references: Cancer Cell. 2008 Oct 7;14(4):312-23
references: 18835033
references: Cell. 2004 Oct 1;119(1):75-86
references: 15454082
references: PLoS Biol. 2009 Nov;7(11):e1000245
references: 19924292
references: Nature. 2003 May 15;423(6937):293-8
references: 12714972
references: Nat Rev Drug Discov. 2008 Oct;7(10):841-53
references: 18827827
references: Nat Rev Drug Discov. 2006 Sep;5(9):769-84
references: 16955068
references: Nat Med. 2005 Jul;11(7):780-5
references: 15980864
references: Mol Cell Biol. 2000 May;20(9):2996-3003
references: 10757784
references: Mol Cell. 2003 Dec;12(6):1599-606
references: 14690611
references: Nat Cell Biol. 2009 Nov;11(11):1376-82
references: 19783983
references: Nat Immunol. 2004 Mar;5(3):309-16
references: 14985714
references: Nature. 2003 Apr 17;422(6933):726-30
references: 12692563
references: Hum Mol Genet. 2005 Oct 15;14(20):2959-69
references: 16126733
references: Curr Opin Chem Biol. 2005 Oct;9(5):431-40
references: 16122969
references: Biochim Biophys Acta. 2010 Aug;1804(8):1626-34
references: 19897059
references: Nat Genet. 2002 May;31(1):94-9
references: 11923874
references: Lancet. 2003 Aug 9;362(9382):440-5
references: 12927431
references: PLoS Biol. 2009 Feb 17;7(2):e36
references: 19226189
references: Am J Med Genet A. 2006 Dec 1;140(23):2603-24
references: 16838330
references: J Biol Chem. 1999 Jun 25;274(26):18341-50
references: 10373438
references: Aging Cell. 2010 Dec;9(6):971-8
references: 20961390
references: Trends Ecol Evol. 1999 Nov;14(11):438-442
references: 10511720
references: Proc Natl Acad Sci U S A. 1959 Jan;45(1):30-45
references: 16590351
references: Nat Rev Cancer. 2003 Mar;3(3):169-78
references: 12612652
references: Cell Cycle. 2006 Sep;5(17):1940-5
references: 16940754
references: Immunity. 2007 Oct;27(4):561-71
references: 17936034
references: Mol Cell Biol. 1999 Jun;19(6):4366-78
references: 10330177
references: EMBO J. 2009 Jan 21;28(2):99-111
references: 19078966
references: Nat Struct Mol Biol. 2007 Nov;14(11):989-96
references: 17984961
references: Br J Pharmacol. 2004 May;142(2):231-55
references: 15155533
references: Genes Dev. 2000 Apr 15;14(8):907-12
references: 10783163
references: Cytogenet Cell Genet. 1981;30(2):92-107
references: 7273860
references: J Cell Sci. 2006 Aug 15;119(Pt 16):3265-72
references: 16899817
references: Science. 2004 Jan 16;303(5656):343-8
references: 14645854
references: Nat Genet. 1997 Sep;17(1):100-3
references: 9288107
references: Nature. 2009 Jul 30;460(7255):587-91
references: 19641587
references: Science. 2004 Apr 2;304(5667):93-6
references: 15064416
references: J Biol Chem. 2002 May 24;277(21):18291-302
references: 11889123
references: J Biol Chem. 2010 Mar 12;285(11):8340-51
references: 20061378
references: Cell. 2005 Feb 25;120(4):513-22
references: 15734683
references: Cell. 2010 Aug 6;142(3):496-496.e1
references: 20691907
references: Nature. 2003 Jan 30;421(6922):499-506
references: 12556884
references: Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18111-6
references: 15608054
references: Nat Struct Mol Biol. 2011 Jan;18(1):80-4
references: 21131978
references: Biochem Cell Biol. 2004 Aug;82(4):482-9
references: 15284901
references: Cell. 2009 Jan 9;136(1):62-74
references: 19135889
references: Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9793-8
references: 18599449
references: Aging Cell. 2008 Jan;7(1):78-88
references: 18005249
references: J Biol Chem. 2010 Oct 22;285(43):32695-32703
references: 20702418
references: Nature. 2011 Feb 3;470(7332):124-8
references: 21293379
references: Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8076-81
references: 9223317
references: Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12879-84
references: 16129833
references: Cell. 2008 Jul 25;134(2):244-55
references: 18662540
references: J Biol Chem. 2006 May 5;281(18):12580-6
references: 16407196
references: Annu Rev Biochem. 2009;78:273-304
references: 19355820
references: Mol Cell. 2004 Mar 12;13(5):739-50
references: 15023343
references: Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12873-8
references: 16129834
references: Cell. 2006 Aug 11;126(3):503-14
references: 16901784
references: Science. 2006 Mar 17;311(5767):1621-3
references: 16484451
references: Science. 2002 Sep 20;297(5589):2051-3
references: 12242442
references: Science. 2002 May 3;296(5569):922-7
references: 11934988
references: Cell. 1997 Feb 7;88(3):375-84
references: 9039264
references: Nat Struct Mol Biol. 2009 Dec;16(12):1286-93
references: 19915592
references: Nat Genet. 2000 Mar;24(3):318-21
references: 10700192
references: J Cell Sci. 2004 Feb 1;117(Pt 4):515-7
references: 14730007
references: Nature. 2005 Sep 22;437(7058):564-8
references: 16079796
references: J Immunol. 2007 Nov 1;179(9):6064-71
references: 17947680
references: DNA Repair (Amst). 2004 Aug-Sep;3(8-9):781-96
references: 15279764
references: J Exp Med. 2007 Jul 9;204(7):1717-27
references: 17606631
references: Mol Cell. 1998 Apr;1(5):707-18
references: 9660954
references: Nat Cell Biol. 2011 Mar;13(3):292-302
references: 21336312
references: Cell. 2005 Jul 1;121(7):973-6
references: 15989948
references: Nat Cell Biol. 2006 Aug;8(8):870-6
references: 16862143
references: Cytogenet Cell Genet. 2000;91(1-4):180-5
references: 11173853
references: Exp Cell Res. 2010 Oct 15;316(17):2747-59
references: 20599958
references: Aging (Albany NY). 2010 May;2(5):274-84
references: 20519774
references: Mol Biol Cell. 2008 Dec;19(12):5238-48
references: 18843043
references: Curr Opin Genet Dev. 2006 Apr;16(2):104-11
references: 16504499
references: Nature. 2005 Nov 17;438(7066):379-83
references: 16292314
references: Biochem J. 2009 Sep 25;423(2):157-68
references: 19772495
references: Nature. 2004 Jun 24;429(6994):891-5
references: 15215866
references: Nature. 2007 Jun 21;447(7147):951-8
references: 17581578
references: Cell. 1996 Jul 12;86(1):159-71
references: 8689683
references: Trends Genet. 2006 Dec;22(12):671-7
references: 16997415
references: EMBO J. 2010 Apr 21;29(8):1434-45
references: 20224553
references: Genes Dev. 1999 Oct 1;13(19):2570-80
references: 10521401
references: Nat Cell Biol. 2009 Oct;11(10):1261-7
references: 19734887
references: Nat Genet. 1998 Oct;20(2):114-6
references: 9771700
references: Mol Cell Biol. 2010 Nov;30(22):5335-47
references: 20837706
references: J Biol Chem. 2010 Jul 2;285(27):20818-26
references: 20439468
references: Genes Dev. 2009 May 15;23(10):1177-82
references: 19451218
references: J Biol Chem. 2005 Apr 29;280(17):17038-45
references: 15684413
references: Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8963-8
references: 15184648
references: N Engl J Med. 2009 Oct 8;361(15):1475-85
references: 19812404
references: Nature. 2009 Jun 11;459(7248):802-7
references: 19516333
references: Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12325-30
references: 21746928
references: Nature. 2006 Jul 27;442(7101):466-70
references: 16799570
references: J Immunol. 2005 Feb 15;174(4):2420-8
references: 15699179
references: Curr Biol. 2001 Jan 23;11(2):105-9
references: 11231126
references: Science. 1996 Jul 26;273(5274):513-6
references: 8662543
references: Science. 2010 May 7;328(5979):753-6
references: 20448184
references: Nat Rev Cancer. 2003 Mar;3(3):155-68
references: 12612651
references: Nature. 2008 Mar 27;452(7186):492-6
references: 18337721
references: Mol Cell. 2000 Nov;6(5):975-87
references: 11106738
references: Nature. 2008 May 29;453(7195):682-6
references: 18438399
references: Development. 1998 Oct;125(20):4007-17
references: 9735362
references: Cell. 2001 Nov 2;107(3):323-37
references: 11701123
references: J Biol Chem. 2002 Oct 18;277(42):39195-201
references: 12154089
references: Cell. 2004 Dec 17;119(6):777-88
references: 15607975
references: Aging Cell. 2006 Oct;5(5):413-22
references: 16939484
references: Nat Immunol. 2004 Aug;5(8):853-61
references: 15258579
references: Biochim Biophys Acta. 2009 Oct;1790(10):963-9
references: 19344750
references: Nature. 2007 Sep 27;449(7161):478-82
references: 17713479
references: Carcinogenesis. 2009 Jan;30(1):2-10
references: 18978338
references: Nat Rev Mol Cell Biol. 2012 Mar 07;13(4):225-238
references: 22395773
references: Curr Opin Genet Dev. 2003 Apr;13(2):136-42
references: 12672490
references: Genes Dev. 2005 Apr 1;19(7):804-14
references: 15774717
references: Cell. 2007 Nov 30;131(5):887-900
references: 18001824
references: Mol Cell Biol. 2011 May;31(10):1972-82
references: 21383063
references: J Biol Chem. 2007 Sep 7;282(36):26132-9
references: 17617668
references: Cell. 1995 Mar 10;80(5):813-23
references: 7889575
references: Genes Dev. 1998 Nov 1;12(21):3382-93
references: 9808625
references: Genes Dev. 2009 May 15;23(10):1171-6
references: 19451217
references: Cell. 2002 Nov 1;111(3):369-79
references: 12419247
references: Mol Cell. 2007 Dec 14;28(5):739-45
references: 18082599
references: Nature. 2005 Aug 4;436(7051):660-5
references: 16079837
references: Mol Cell Biol. 2003 Jan;23(1):38-54
references: 12482959
references: Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10794-9
references: 12960381
references: Cell. 1999 Jun 25;97(7):833-42
references: 10399912
references: Cell. 2008 Oct 3;135(1):85-96
references: 18854157
references: J Med Genet. 2004 Sep;41(9):715-7
references: 15342704
references: Cell Cycle. 2009 Aug 15;8(16):2662-3
references: 19597350
references: J Clin Invest. 2008 Oct;118(10):3291-300
references: 18769635
references: Trends Biochem Sci. 2010 Feb;35(2):101-8
references: 19875294
references: Mutat Res. 2007 May 1;618(1-2):65-80
references: 17291544
references: Nat Med. 2005 Apr;11(4):440-5
references: 15750600
references: Mol Endocrinol. 2006 Oct;20(10):2432-43
references: 16728531
references: Nat Rev Mol Cell Biol. 2006 Jun;7(6):437-47
references: 16723979
references: Mol Cell Biol. 2005 May;25(10):3934-44
references: 15870268
references: EMBO J. 2004 Mar 24;23(6):1348-59
references: 15014446
references: Aging Cell. 2007 Dec;6(6):759-67
references: 17877786
references: Nat Chem Biol. 2007 Oct;3(10):640-9
references: 17876321
references: Mol Cell Biol. 2011 Oct;31(19):3924-37
references: 21807899
references: Mech Ageing Dev. 2005 Jan;126(1):71-7
references: 15610764
references: J Exp Med. 2004 Nov 1;200(9):1103-10
references: 15520243
references: Nat Cell Biol. 2006 Jan;8(1):91-9
references: 16341205
references: J Alzheimers Dis. 2009;18(1):131-9
references: 19625751
references: Nature. 1999 Aug 19;400(6746):784-7
references: 10466730
references: Mol Cell. 2010 Oct 22;40(2):179-204
references: 20965415
references: EMBO J. 2001 Oct 15;20(20):5791-801
references: 11598021
references: Mol Cell. 1998 Dec;2(6):851-61
references: 9885572
references: J Biol Chem. 2000 Sep 15;275(37):28349-52
references: 10880505
references: Mutat Res. 2007 May 1;618(1-2):18-29
references: 17316710
references: J Cell Sci. 2006 Nov 15;119(Pt 22):4644-9
references: 17062639
references: Mol Biol Cell. 1999 Aug;10(8):2655-68
references: 10436020
references: Mol Cell Biol. 2007 Oct;27(20):7028-40
references: 17709392
references: J Biol Chem. 2000 Mar 31;275(13):9636-44
references: 10734115
references: Cell Metab. 2011 Aug 3;14(2):161-72
references: 21803287
references: Cell Metab. 2008 Oct;8(4):333-41
references: 18840364
references: Nat Rev Mol Cell Biol. 2010 Mar;11(3):171-81
references: 20125188
references: Science. 2010 Feb 12;327(5967):836-40
references: 20044539
references: PLoS Biol. 2009 Feb 17;7(2):e35
references: 19226188
references: Nature. 2005 Nov 17;438(7066):374-8
references: 16292313
references: Mech Dev. 2001 Sep;107(1-2):141-53
references: 11520670
references: Science. 1996 Apr 12;272(5259):258-62
references: 8602509
references: Nature. 2003 Oct 30;425(6961):962-7
references: 14574365
references: J Exp Med. 1998 Jun 15;187(12):2081-9
references: 9625768
references: EMBO J. 2009 Sep 2;28(17):2616-24
references: 19644444
references: Nat Rev Mol Cell Biol. 2009 Jun;10(6):373-84
references: 19424290
references: Br J Cancer. 2007 Mar 12;96(5):686-91
references: 17311013
references: Curr Opin Genet Dev. 2006 Apr;16(2):151-6
references: 16503135
references: Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13015-20
references: 11078522
references: Cell. 2006 Jan 27;124(2):301-13
references: 16439205
references: Cell. 1996 Dec 27;87(7):1249-60
references: 8980231
references: Leukemia. 2007 Feb;21(2):195-200
references: 17151702
references: Annu Rev Immunol. 2008;26:261-92
references: 18370922
references: Clin Genet. 2004 Nov;66(5):375-81
references: 15479179
references: Circ Res. 2007 May 25;100(10):1512-21
references: 17446436
references: Nucleus. 2010 Nov-Dec;1(6):472-4
references: 21327088
references: Nature. 1999 Sep 23;401(6751):397-9
references: 10517641
references: Cell. 1999 Feb 5;96(3):389-92
references: 10025404
references: Cell Res. 2011 Mar;21(3):396-420
references: 21358755
references: Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11472-7
references: 9326634
references: Nat Cell Biol. 2009 Jan;11(1):92-6
references: 19079244
references: Nat Cell Biol. 2009 Jul;11(7):865-72
references: 19525936
references: Cell. 2003 Jun 13;113(6):703-16
references: 12809602
references: Science. 2006 Feb 10;311(5762):844-7
references: 16469925
references: Nat Rev Mol Cell Biol. 2005 Feb;6(2):139-49
references: 15688000
references: Mol Cell. 2010 Nov 24;40(4):594-605
references: 21095589
references: Cell. 2009 Feb 6;136(3):420-34
references: 19203578
references: Nat Rev Mol Cell Biol. 2005 Oct;6(10):757-65
references: 16167054
references: Aging Cell. 2008 Jun;7(3):355-67
references: 18363904
references: J Med Genet. 2004 Apr;41(4):304-8
references: 15060110
references: Cell Cycle. 2009 Aug 15;8(16):2664-6
references: 19625767
references: Science. 1974 May 24;184(4139):868-71
references: 4825889
references: Cell. 2006 Jan 27;124(2):315-29
references: 16439206
references: Nat Med. 2008 Jul;14(7):767-72
references: 18587406
references: Mol Cell Biol. 2010 Jul;30(14):3582-95
references: 20479123
references: J Biol Chem. 1998 Mar 6;273(10):5858-68
references: 9488723
references: Science. 2009 Jan 16;323(5912):373-5
references: 19074312
references: EMBO J. 1998 Apr 15;17(8):2404-11
references: 9545251
references: Nature. 2003 Nov 13;426(6963):194-8
references: 14608368
references: Mol Cell Biol. 2007 Dec;27(24):8502-9
references: 17923702
references: J Biol Chem. 2005 Apr 29;280(17):17187-95
references: 15749705
references: EMBO J. 2007 Sep 19;26(18):4113-25
references: 17762868