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Core and Linker Histone Modifications Involved in the DNA Damage Response

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Genome Stability and Human Diseases

Part of the book series: Subcellular Biochemistry ((SCBI,volume 50))

Abstract

The stability of the genome is constantly under attack from both endogenous and exogenous DNA damaging agents. These agents, as well as naturally occurring processes such as DNA replication and recombination can result in DNA double-strand breaks (DSBs). DSBs are potentially lethal and so eukaryotic cells have evolved an elaborate pathway, the DNA damage response, which detects the damage, recruits proteins to the DSBs, activates checkpoints to stall cell cycle progression and ultimately mediates repair of the damaged DNA. As the DSBs occur in the context of chromatin, execution of this response is partly orchestrated through the modification of the DNA-bound histone proteins. These histone modifications include the addition or removal of various chemical groups or small peptides and function to change the chromatin structure or to attract factors involved in the DNA damage response, and as such, are particularly important in the early stages of the DNA damage response. This review will focus on such modifications, the enzymes responsible and also highlights their importance by reporting known roles for these modifications in genome stability and disease.

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Abbreviations

53BP1:

p53 binding protein 1

ABRA1:

Abraxas-BRCA1-A complex subunit

ac:

acetylated

ADP:

adenosine di-phosphate

AF4:

ALL1 fused gene from chromosome 4

ASF1A:

anti-silencing function 1A

ATM:

ataxia telangiectasia mutated

ATR:

ATM and Rad3-related

BRCA1:

breast cancer 1 early onset

BRCT:

BRCA1 c-terminal

CAF-1:

chromatin assembly factor 1

CBP/p300:

CREB binding protein/Histone acetyltransferase p300

ChIP:

chromatin immunoprecipitation

Chk1:

checkpoint kinase 1

Chk2:

checkpoint kinase 2

Crb2:

crumbs homologue 2 (Rad9 homologue)

DDR:

DNA damage response

DNA:

deoxy-ribonucleic acid

DNA-PK:

DNA dependent protein kinase

DSB:

double strand break

DUB:

deubiquitinase

E:

Glutamic acid

ES:

embryonic stem

EYA:

eyes absent homologue

FHA:

forkhead associated

FRAP:

fluorescence recovery after photobleaching

grp :

grapes (Drosophila Chk1)

H1:

Histone 1

H2A:

Histone 2A

H2B:

Histone 2B

H2AX:

Histone 2A.X

H3:

Histone 3

H4:

Histone 4

H2Av:

Histone 2Av

HDAC:

histone deacetylase

hMOF:

human MOF (a.k.a. KAT8)

HP1:

heterochromatin protein 1

HP1-β:

heterochromatin protein 1 beta

HR:

homologous recombination

IR:

ionizing radiation

JNK1:

Jun N-terminal kinase

K:

Lysine

KAT:

lysine acetyltransferase

KDM:

lysine demethylase

KMT:

lysine methyltransferase

LOH:

loss of heterozygosity

lok :

long form of nuclear kinase (Drosophila Chk2)

MDC1:

mediator of DNA checkpoint 1

me:

methylated

MEF:

mouse embryonic fibroblast

MIU:

motif interacting with ubiquitin

MOF:

males absent on the first

MRN:

Mre11-Rad50-Nbs1

NBS1:

Nijmegen breakage syndrome 1

NHEJ:

non-homologous end joining

ph:

phosphorylated

PIKK:

phosphatidylinositol-3 kinase related kinase

PRMT:

protein arginine methyltransferase

Q:

Glutamine

R:

Arginine

Rad51:

radiation (sensitive) 51

RAP80:

receptor associated protein 80

RNAi:

RNA interference

RNF168:

ring finger protein 168

RNF8:

ring finger protein 8

ROS:

reactive oxygen species

S:

Serine

SIRT1:

silent mating type information regulation homologue 1

SIRT2:

silent mating type information regulation homologue 2

SNF2H:

sucrose non-fermenting protein 2 homologue

Su(var)3-9:

suppressor of variegation 3-9

SUMO:

small ubiquitin-like modifier

SUV39H:

suppressor of variegation 3-9 homologue (human)

T:

Threonine

Tip60:

HIV Tat-interacting protein 60 kDa (a.k.a. KAT5)

Trrap:

transformation/transcription domain-associated protein

ub:

ubiquitin

UBC13:

ubiquitin conjugating enzyme E2 13

UIM:

ubiquitin interaction motif

WICH:

WSTF-ISWI chromatin remodelling

WSTF:

William’s syndrome transcription factor

Y:

Tyrosine

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Acknowledgements

We thank Ciaran Morrison and members of the lab for critical reading of the manuscript. Work in the Rea laboratory is supported by a Science Foundation Ireland President of Ireland Young Researcher Award (SFI-PIYRA), 07/Y14/I1052.

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  1. Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland, University Rd, Galway, Ireland

    Jennifer E. Chubb & Stephen Rea

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  1. Jennifer E. Chubb
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    Heinz-Peter Nasheuer

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Chubb, J.E., Rea, S. (2010). Core and Linker Histone Modifications Involved in the DNA Damage Response. In: Nasheuer, HP. (eds) Genome Stability and Human Diseases. Subcellular Biochemistry, vol 50. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3471-7_2

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