Mammalian single-strand break repair: Mechanisms and links with chromatin
Section snippets
The detection of SSBs
SSBR can be divided into four basic steps, beginning with SSB detection and signaling (Fig. 1A). This appears to be achieved by poly (ADP-ribose) polymerase-1 (PARP-1) and possibly also poly (ADP-ribose) polymerase-2 (PARP-2), which rapidly bind to and are activated by DNA strand breaks ([1], [2], [3], and reviewed in [4]). Once activated, PARP-1 covalently modifies itself and other target proteins with long chains of negatively charged poly ADP-ribose (PAR) [4], [5]. The binding and activity
Replication-coupled SSBR
As discussed above, the XRCC1–Lig3α interaction is partly or largely dispensable for XRCC1-dependent repair of EMS-induced SSBs during S/G2 [100], [101], [102]. Consequently, we have proposed that in addition to the rapid SSBR process(es) that presumably operate throughout interphase, S/G2 phase cells possess an additional, XRCC1-dependent, SSBR process that is intimately linked to DNA replication and which we have termed replication-coupled SSBR (RC-SSBR) [107], [108]. Moreover, the
SSBs and chromatin
Within chromosomes, each 147 base pairs of DNA is wrapped ∼1.6 times around a histone octamer comprised of two molecules each of the histones H2A, H2B, H3, and H4, creating a structure known as the nucleosome. In addition, chromatin is packaged into higher order fibres that further compact DNA. While in recent years there has been an explosion of papers describing the impact of chromatin structure on the detection and repair of UV damage and DNA double-strand breaks, little is known about the
References (157)
- et al.
Poly(ADP-ribose) synthesis in vitro programmed by damaged DNA. A comparison of DNA molecules containing different types of strand breaks
J. Biol. Chem.
(1980) - et al.
PARP-2, a novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase
J. Biol. Chem.
(1999) - et al.
Bovine thymus poly(adenosine diphosphate ribose) polymerase. Physical properties and binding to DNA
J. Biol. Chem.
(1980) - et al.
Poly(ADP-ribose) synthetase, a main acceptor of poly(ADP-ribose) in isolated nuclei
J. Biol. Chem.
(1981) - et al.
Poly(ADP-ribosylation) in vitro. Reaction parameters and enzyme mechanism
J. Biol. Chem.
(1982) - et al.
Prolongation of the p53 response to DNA strand breaks in cells depleted of PARP by antisense RNA expression
Biochem. Biophys. Res. Commun.
(1998) - et al.
Poly(ADP-ribose) polymerase-1 (PARP-1) is required in murine cell lines for base excision repair of oxidative DNA damage in the absence of DNA polymerase beta
J. Biol. Chem.
(2003) - et al.
DNA polymerase beta-mediated long patch base excision repair. Poly(ADP-ribose)polymerase-1 stimulates strand displacement DNA synthesis
J. Biol. Chem.
(2001) - et al.
Down-regulation of DNA repair synthesis at DNA single-strand interruptions in poly(ADP-ribose) polymerase-1 deficient murine cell extracts
DNA Repair (Amst.)
(2002) - et al.
ATP for the DNA ligation step in base excision repair is generated from poly(ADP-ribose)
J. Biol. Chem.
(2000)
ATP-dependent selection between single nucleotide and long patch base excision repair
DNA Repair (Amst.)
Post-translational modification of poly(ADP-ribose) polymerase induced by DNA strand breaks
Trends Biochem. Sci.
Two pathways for base excision repair in mammalian cells
J. Biol. Chem.
Proliferating cell nuclear antigen facilitates excision in long-patch base excision repair
J. Biol. Chem.
DNA polymerase beta and flap endonuclease 1 enzymatic specificities sustain DNA synthesis for long patch base excision repair
J. Biol. Chem.
AP endonuclease-independent DNA base excision repair in human cells
Mol. Cell
Base excision repair of oxidative DNA damage activated by XPG protein
Mol. Cell
XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair
Cell
Molecular cloning of the human gene, PNKP, encoding a polynucleotide kinase 3′-phosphatase and evidence for its role in repair of DNA strand breaks caused by oxidative damage
J. Biol. Chem.
Molecular characterization of a human DNA kinase
J. Biol. Chem.
Association of XRCC1 and tyrosyl DNA phosphodiesterase (Tdp1) for the repair of topoisomerase I-mediated DNA lesions
DNA Repair (Amst.)
DNA single-strand breaks and neurodegeneration
DNA Repair (Amst.)
Repair of and checkpoint response to topoisomerase I-mediated DNA damage
Mutat. Res.
Conversion of phosphoglycolate to phosphate termini on 3′ overhangs of DNA double strand breaks by the human tyrosyl-DNA phosphodiesterase hTdp1
J. Biol. Chem.
Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkages
J. Biol. Chem.
DNA single-strand break repair and spinocerebellar ataxia
Cell
The role of yeast DNA 3′-phosphatase Tpp1 and rad1/Rad10 endonuclease in processing spontaneous and induced base lesions
J. Biol. Chem.
The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks
Cell
Human RAD2 homolog 1 5′- to 3′-exo/endonuclease can efficiently excise a displaced DNA fragment containing a 5′-terminal abasic lesion by endonuclease activity
J. Biol. Chem.
Excision repair and DNA synthesis with a combination of HeLa DNA polymerase beta and DNase V
J. Biol. Chem.
DNA polymerase beta conducts the gap-filling step in uracil-initiated base excision repair in a bovine testis nuclear extract
J. Biol. Chem.
Evidence that DNA polymerases alpha and beta participate differentially in DNA repair synthesis induced by different agents
J. Biol. Chem.
The roles of DNA polymerases alpha, beta, and gamma in DNA repair synthesis induced in hamster and human cells by different DNA damaging agents
J. Biol. Chem.
Two different mechanisms are involved for the bleomycin-induced DNA repair synthesis in permeabilized HeLa cells
Biochem. Biophys. Res. Commun.
Reconstitution of proliferating cell nuclear antigen-dependent repair of apurinic/apyrimidinic sites with purified human proteins
J. Biol. Chem.
Oxygen radical-induced single-strand DNA breaks and repair of the damage in a cell-free system
Mutat. Res.
Gap-filling DNA synthesis by HeLa DNA polymerase alpha in an in vitro base excision DNA repair scheme
J. Biol. Chem.
Specific interaction of DNA polymerase beta and DNA ligase I in a multiprotein base excision repair complex from bovine testis
J. Biol. Chem.
Role of DNA polymerase beta in the excision step of long patch mammalian base excision repair
J. Biol. Chem.
FEN1 stimulation of DNA polymerase beta mediates an excision step in mammalian long patch base excision repair
J. Biol. Chem.
Aphidicolin-resistant and -sensitive base excision repair in wild-type and DNA polymerase beta-defective mouse cells
DNA Repair (Amst.)
DNA polymerase lambda, a novel DNA repair enzyme in human cells
J. Biol. Chem.
Identification of an intrinsic 5′-deoxyribose-5-phosphate lyase activity in human DNA polymerase lambda: a possible role in base excision repair
J. Biol. Chem.
DNA polymerase lambda protects mouse fibroblasts against oxidative DNA damage and is recruited to sites of DNA damage/repair
J. Biol. Chem.
DNA polymerase lambda mediates a back-up base excision repair activity in extracts of mouse embryonic fibroblasts
J. Biol. Chem.
DNA ligases in the repair and replication of DNA
Mutat. Res.
Involvement of XRCC1 and DNA ligase III gene products in DNA base excision repair
J. Biol. Chem.
Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions
Biochem. J.
A shuttle mechanism for DNA–protein interactions. The regulation of poly(ADP-ribose) polymerase
Eur. J. Biochem.
Base excision repair is efficient in cells lacking poly(ADP-ribose) polymerase 1
Nucl. Acids Res.
Cited by (128)
Advances in enzyme-free nucleic acid amplification-based fluorescent biosensors for real-time imaging of DNA repair enzymes in living cells
2023, Coordination Chemistry ReviewsDNA repair mechanisms: Exploring potentials of nutraceutical
2023, Journal of Functional FoodsDamage-Net: A program for DNA repair meta-analysis identifies a network of novel repair genes that facilitate cancer evolution
2021, DNA RepairCitation Excerpt :The major DNA repair pathways include base excision repair (BER), nucleotide excision repair (NER), single-strand break repair (SSBR) and double-strand break repair (DSBR) [1,2]. BER repairs non-bulky DNA adducts, such as oxidised nucleotides [3], NER repairs bulky, helix distorting DNA adducts [4], SSBR repairs single-strand cuts in the double-helix [5] and DSBR functions via multiple downstream repair pathways, predominantly non-homologous end-joining (NHEJ) and homologous recombination (HR) [6]. Despite these highly complex and efficient repair pathways, DNA repair is imperfect and can therefore lead to the formation of mutations throughout our genomes [7,8].