Base damage and single-strand break repair: Mechanisms and functional significance of short- and long-patch repair subpathways

Fortini, Paola; Dogliotti, Eugenia

doi:10.1016/j.dnarep.2006.10.008

Cited by 272 publications

(203 citation statements)

References 95 publications

Supporting

Mentioning

198

Contrasting

Order By: Relevance

“…If not repaired, it can disrupt transcription and replication and can be converted into potentially clastogenic and/or lethal DSBs. This DNA damage is repaired via SSBR pathway (101,102). SSBR pathway includes four basic steps: a. SSB detection and signaling, through poly (ADPribose) polymerase (PARP); b. DNA break end processing, through the role of polynucleotide kinase (PNK), AP endonuclease-1 (APE1), DNA polymerase β (Pol β), tyrosyl phosphodiesterase 1 (TDP1), and flap endonuclease-1 (FEN-1); c. gap filling, involving in multiple DNA polymerases; d. DNA ligation, involving in multiple DNA ligases.…”

Section: Genetic Polymorphisms In Genes Involved In Ssbr Pathway and mentioning

confidence: 99%

DNA Repair Capacity-Related to Genetic Polymorphisms of DNA Repair Genes and Aflatoxin B1-Related Hepatocellular Carcinoma Among Chinese Population

Long¹,

Yao²,

Zeng³

et al. 2011

DNA Repair

View full text Add to dashboard Cite

Section: Genetic Polymorphisms In Genes Involved In Ssbr Pathway and mentioning

confidence: 99%

DNA Repair Capacity-Related to Genetic Polymorphisms of DNA Repair Genes and Aflatoxin B1-Related Hepatocellular Carcinoma Among Chinese Population

Long¹,

Yao²,

Zeng³

et al. 2011

DNA Repair

View full text Add to dashboard Cite

“…AAG recognizes the damaged base and initiates the base excision repair (BER) process by cleaving the N-glycosylic bond between the damaged base and the deoxyribose, creating an abasic site [2,4]. In its simplest form, BER is completed by the action of AP endonuclease (APE1 in human) which cleaves at the abasic site, DNA polymerase β which trims the 5' end and fills in the missing nucleotide, and DNA ligase which seals the nick [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

3-Methyladenine DNA glycosylase is important for cellular resistance to psoralen interstrand cross-links

et al. 2008

View full text Add to dashboard Cite

DNA interstrand cross-links (ICLs), widely used in chemotherapy, are cytotoxic lesions because they block replication and transcription. Repair of ICLs involves proteins from different repair pathways however the precise mechanism is still not completely understood. Here, we report that the 3-methyladenine DNA glycosylase (Aag), an enzyme that initiates base excision repair at a variety of alkylated bases, is also involved plays a role in the repair of ICLs. Aag−/− mouse embryonic stem cells were shown to be more sensitive to the cross-linking agent 4, 5', 8-trimethylpsoralen than wildtype cells, but no more sensitive than wild-type to the psoralen derivative Angelicin that forms only monoadducts. We show that γ-H2AX foci formation, a marker for double strand breaks that are formed during ICL repair, is impaired in psoralen treated Aag−/− cells in both quantity and kinetics. However, in our in vitro system, purified human AAG can neither bind to the ICL nor cleave it. Taken together, our results suggest that Aag is important for the resistance of mouse ES cells to psoralen-induced ICLs. has a role in the repair of ICLs in mouse ES cells, but that its involvement may be indirect, perhaps mediated through interaction with other proteins, or by its action on an intermediate of ICL repair.

show abstract

“…Free radicals produce various types of abasic lesions. Two subpathways, shortand long-patch BER, restore the template by replacement of one or more nucleotides at the lesion site, respectively (2). Therefore, the BER pathways should play a key role in the control of muscle cell integrity.…”

mentioning

confidence: 99%

Terminally differentiated muscle cells are defective in base excision DNA repair and hypersensitive to oxygen injury

Narciso

Fortini

Pajalunga

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

107

View full text Add to dashboard Cite

The differentiation of skeletal myoblasts is characterized by permanent withdrawal from the cell cycle and fusion into multinucleated myotubes. Muscle cell survival is critically dependent on the ability of cells to respond to oxidative stress. Base excision repair (BER) is the main repair mechanism of oxidative DNA damage. In this study, we compared the levels of endogenous oxidative DNA damage and BER capacity of mouse proliferating myoblasts and their differentiated counterpart, the myotubes. Changes in the expression of oxidative stress marker genes during differentiation, together with an increase in 8-hydroxyguanine DNA levels in terminally differentiated cells, suggested that reactive oxygen species are produced during this process. The repair of 2-deoxyribonolactone, which is exclusively processed by longpatch BER, was impaired in cell extracts from myotubes. The repair of a natural abasic site (a preferred substrate for short-patch BER) also was delayed. The defect in BER of terminally differentiated muscle cells was ascribed to the nearly complete lack of DNA ligase I and to the strong down-regulation of XRCC1 with subsequent destabilization of DNA ligase III␣. The attenuation of BER in myotubes was associated with significant accumulation of DNA damage as detected by increased DNA single-strand breaks and phosphorylated H2AX nuclear foci upon exposure to hydrogen peroxide. We propose that in skeletal muscle exacerbated by free radical injury, the accumulation of DNA repair intermediates, due to attenuated BER, might contribute to myofiber degeneration as seen in sarcopenia and many muscle disorders.oxidative stress ͉ XRCC1 ͉ DNA ligases ͉ DNA single-strand breaks ͉ 8-oxoguanine

show abstract

Base damage and single-strand break repair: Mechanisms and functional significance of short- and long-patch repair subpathways

Cited by 272 publications

References 95 publications

DNA Repair Capacity-Related to Genetic Polymorphisms of DNA Repair Genes and Aflatoxin B1-Related Hepatocellular Carcinoma Among Chinese Population

DNA Repair Capacity-Related to Genetic Polymorphisms of DNA Repair Genes and Aflatoxin B1-Related Hepatocellular Carcinoma Among Chinese Population

3-Methyladenine DNA glycosylase is important for cellular resistance to psoralen interstrand cross-links

Terminally differentiated muscle cells are defective in base excision DNA repair and hypersensitive to oxygen injury

Contact Info

Product

Resources

About