DNA repair - what is it? and why is it important?

Our DNA is constantly accumulating damage from many sources. If left unrepaired, this damage can result in mutations and ultimately in cancer. Consequently, all life on earth has evolved mechanisms in order to repair DNA damage. There are several different DNA repair mechanisms, each specific for a different type of damage. Defects in any of these DNA repair pathways can contribute to the development of specific cancers and other diseases.

(summarised in table below)

DNA damaging agent	Type of damage	Repair mechanism(s)	Related diseases
ionising radiation (e.g. x-rays) oxidative intermediates	double strand breaks (DSB)	recombinational repair (RR) non-homologous end-joining (NHEJ)	breast cancer
UV, ionising radiation, oxidative and alkylating agents	base damage	base excision repair (BER)	embryonic lethality premature aging lung cancer (?) hereditary breast cancer (?)
UV and chemical carcinogens	bulky lesions	nucleotide excision repair (NER)	skin cancer
replication errors	DNA mismatches	mismatch repair (MMR)	hereditary colon cancer

AT	ataxia telangiectasia	a genetic disorder characterised by extreme sensitivity to IR
BER	base excision repair	mechanism for removal of alkylation and oxidative base damage
BRCA	breast cancer gene	name for 2 genes (BRCA1 and BRCA2) implicated in hereditary breast cancer
CS	Cockayne syndrome	genetic disorder arising from deficiency in TCR aspects of both NER and BER and/or transcription.
DNA	deoxyribonucleic acid	basic genetic material
DSB	double strand breaks	lesion in which both sugar-phosphate strands of a DNA molecule are broken
GGR	global genome repair	repair of all DNA in cell irresoective of transcription status (contrast with TCR)
IR	ionising radiation	high energy radiations (such as x-rays and g-rays) which are capable of ejecting one or more orbital electrons from an atom or molecule.
MMR	mismatch repair	mechanism for repair of mismatched base pairs, which generally arise from errors during DNA replication
NER	nucleotide excision repair	mechanism for repair of "bulky" helix-distorting lesions, such as damage induced by UV
NHEJ	non-homologous end-joining	mechanism for repair of DSB, in which DNA ends are directly rejoined
pol	polymerase	an enzyme which replicates DNA (DNA pol) or synthesises RNA (RNA pol) from an existing DNA template.
RNA	ribonucleic acid	A chemical similar to a single strand of DNA, which serves as a template for protein synthesis. The sequence of a strand of mRNA is based on the sequence of a complementary strand of DNA.
RR	recombinational repair	mechanism for repair of DSB, using homologous DNA as a template
TCR	transcription coupled repair	a sub-pathway of BER and NER which rapidly repairs active genes (contrast with GGR)
TTD	trichothiodystophy	genetic disorder similar to CS
XP	xeroderma pigmentosum	genetic disorder arising from defect in NER (can overlap with CS and/or TTD in some cases)

1.	DNA Repair (What is it? and Why is it important?)
	Overview of DNA damage, DNA repair mechanisms and related diseases Table of contents List of abbreviations Summary of relevant links


2.	What is DNA? (a brief introduction / review)
	DNA structure Transcription and translation Transcription-coupled repair (TCR) vs. global genome repair (GGR) Cell cycle


3.	Ultraviolet radiation and skin cancer
	Skin cancer incidence Relationship between UV exposure and skin cancer The UV spectrum, types of DNA damage induced, and relative cancer risk Oxidative DNA damage DNA photoproducts induced by UV-B and UV-C


4.	Nucleotide excision repair (NER)
	Prokaryotic NER Transcription-coupled repair in prokaryotes Human genetic disorders characterised by NER deficiencies Xeroderma pigmentosum Cockayne syndrome Trichothiodystrophy Eukaryotic NER Identification of human NER genes Lesion recognition Assembly of pre-incision complexes (PICs) Transcription-coupled repair in eukaryotes Dual roles for XPF / ERCC1 ?
5.	Tables of NER proteins
	I. Clinical characteristics of NER deficient disorders II. Roles of NER proteins III. Evolutionary conservation of NER proteins


6.	Alternative mechanisms for repairing UV-induced photoproducts
	Direct reversion of UV-induced photoproducts Glycosylases specific for UV-induced DNA damage


7.	Base excision repair (BER)
	Short patch BER Long patch BER Consequences of defective BER Functional overlap of NER and BER pathways


8.	Replicational bypass of DNA damage
	Error-free bypass Error-prone bypass

9.	DNA double strand breaks (DSB)
	DSB repair in humans Non-homologous end-joining (NHEJ) Recombinational repair (RR) IR exposure, DSB and breast cancer Ataxia telangiectasia


10.	Mismatch repair (MMR)
	Prokaryotic MMR Eukaryotic MMR MMR and hereditary colon cancer