Characterization of the XRCC1-DNA ligase III complex<i>in vitro</i>and its absence from mutant hamster cells

Caldecott, Keith W.; Tucker, James D.; Stanker, Lawrence H.; Thompson, Larry H.

doi:10.1093/nar/23.23.4836

Cited by 265 publications

(236 citation statements)

References 27 publications

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“…In contrast to XRCC1 haplodeficient mouse primary B cells (18), deletion of one copy of Xrcc1 in CH12F3 cells does not alter XRCC1 protein levels. Although there is a moderate reduction of Lig3 protein in XRCC1 Δ/Δ cells (consistent with a role of XRCC1 in stabilizing Lig3) (14), Lig3 protein levels in XRCC1 +/Δ cells (Fig. 1C) are indistinguishable from XRCC1 +/+ cells, consistent with the lack of effect haplodeficiency has on XRCC1 expression levels in these cells.…”

Section: Resultssupporting

confidence: 68%

X-ray repair cross-complementing protein 1 (XRCC1) deficiency enhances class switch recombination and is permissive for alternative end joining

Han

Mao

2012

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

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DNA double-strand breaks (DSBs) are essential intermediates in Ig gene rearrangements: V(D)J and class switch recombination (CSR). In contrast to V(D)J recombination, which is almost exclusively dependent on nonhomologous end joining (NHEJ), CSR can occur in NHEJ-deficient cells via a poorly understand backup pathway (or pathways) often termed alternative end joining (A-EJ). Recently, several components of the single-strand DNA break (SSB) repair machinery, including XRCC1, have been implicated in A-EJ. To determine its role in A-EJ and CSR, Xrcc1 was deleted by targeted mutation in the CSR proficient mouse B-cell line, CH12F3. Here we demonstrate that XRCC1 deficiency slightly increases the efficiency of CSR. More importantly, Lig4 and XRCC1 double-deficient cells switch as efficiently as Lig4-deficient cells, clearly indicating that XRCC1 is dispensable for A-EJ in CH12F3 cells during CSR.A DNA double-strand break (DSB) is one of the most severe forms of DNA damage and can result in chromosome loss or translocations. A variety of endogenous and exogenous sources can induce DSBs, including ionizing radiation, reactive oxygen species, and some chemicals. On the other hand, physiological processes during lymphocyte development such as V(D)J and Ig class switch recombination (CSR) rely on DSBs to rearrange genetic information in somatic cells.V(D)J recombination is a site-specific DNA recombination initiated by the RAG proteins, which are evolved from an ancient DNA transposase. The RAG complex recognizes specific DNA sequences called recombination signal sequences (RSS) and cuts the DNA on one side of the RSS. The ensuing repair of the four DNA ends that are produced from a pair of cleavage events results in joining of subexonic coding fragments to form an exon encoding the antigen-binding domain of a B-or T-cell receptor. In contrast, CSR in antigen-stimulated mature B cells is a regionally specific recombination between two repetitive regions [called switch (S) regions] that precede each of the constant regions (1). Looping out intervening sequences between two S regions allows the expression of a new constant region that was further downstream and results in a switch of Ig class (or isotype) from IgM to IgG, IgE, or IgA (2). CSR is initiated by activation-induced cytidine deaminase (AID) that converts DNA cytosines into uracils at S regions. Through mechanisms that are not yet fully understood, repair of AID-generated uracils in the S region ultimately results in DSBs (2), which serve as critical intermediates in an overall cut-and-paste chromosomal deletion (2).In vertebrate cells, DSB repair mechanisms generally fall into two major categories: homologous recombination (HR) and nonhomologous end joining (NHEJ) (3). HR relies on the presence of another copy of DNA sequences that are highly similar to the one harboring the DSB. Copying genetic information from the intact copy allows high-fidelity repair of the DSB. In complex genomes rich in repetitive DNA sequences, HR is restricted to S and G2 phase of the ce...

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Section: Resultssupporting

confidence: 68%

X-ray repair cross-complementing protein 1 (XRCC1) deficiency enhances class switch recombination and is permissive for alternative end joining

Han

Mao

2012

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

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“…XRCC1 is a scaffolding protein that functions in the repair of single-strand breaks, the most common lesions in cellular DNA (Caldecott et al, 1995). ADPRT is an abundant nuclear protein that specifically recognizes and binds DNA strand breaks through two tandem-arrayed N-terminal zinc fingers, and recruits other DNA repair proteins to jointly perform the DNA damage repair .…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of XRCC1 and ADPRT Genes and Risk of Noncardia Gastric Cancer in a Chinese Population: a Case-control Study

Xie¹,

Loh²,

Wen³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…In addition, the interaction of XRCC1 with PNKP has been shown to stimulate both the 5′-kinase and 3′-phosphatase activities of this enzyme [57]. Similarly, XRCC1 interacts with DNA ligase III and increases the intracellular stability of the ligase [58,59]. The association PARP-1 with the XRCC1 complex has also been observed.…”

Section: Tdp1 Repair Pathwaysmentioning

confidence: 96%

Tyrosyl-DNA Phosphodiesterase as a Target for Anticancer Therapy

Dexheimer¹,

Antony²,

Marchand³

et al. 2008

ACAMC

139

201

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Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a recently discovered enzyme that catalyzes the hydrolysis of 3′-phosphotyrosyl bonds. Such linkages form in vivo following the DNA processing activity of topoisomerase I (Top1). For this reason, Tdp1 has been implicated in the repair of irreversible Top1-DNA covalent complexes, which can be generated by either exogenous or endogenous factors. Tdp1 has been regarded as a potential therapeutic co-target of Top1 in that it seemingly counteracts the effects of Top1 inhibitors, such as camptothecin and its clinically used derivatives. Thus, by reducing the repair of Top1-DNA lesions, Tdp1 inhibitors have the potential to augment the anticancer activity of Top1 inhibitors provided there is a presence of genetic abnormalities related to DNA checkpoint and repair pathways. Human Tdp1 can also hydrolyze other 3′-end DNA alterations including 3′-phosphoglycolates and 3′-abasic sites indicating it may function as a general 3′-DNA phosphodiesterase and repair enzyme. The importance of Tdp1 in humans is highlighted by the observation that a recessive mutation in the human TDP1 gene is responsible for the inherited disorder, spinocerebellar ataxia with axonal neuropathy (SCAN1). This review provides a summary of the biochemical and cellular processes performed by Tdp1 as well as the rationale behind the development of Tdp1 inhibitors for anticancer therapy.

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Characterization of the XRCC1-DNA ligase III complexin vitroand its absence from mutant hamster cells

Cited by 265 publications

References 27 publications

X-ray repair cross-complementing protein 1 (XRCC1) deficiency enhances class switch recombination and is permissive for alternative end joining

X-ray repair cross-complementing protein 1 (XRCC1) deficiency enhances class switch recombination and is permissive for alternative end joining

Polymorphisms of XRCC1 and ADPRT Genes and Risk of Noncardia Gastric Cancer in a Chinese Population: a Case-control Study

Tyrosyl-DNA Phosphodiesterase as a Target for Anticancer Therapy

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