DNA repair gets physical: Mapping an XPA-binding site on ERCC1

Croteau, Deborah L.; Ye, Peng; Houten, Bennett Van

doi:10.1016/j.dnarep.2008.01.018

Cited by 26 publications

(27 citation statements)

References 48 publications

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“…These results are consistent with a previous study that examined a recombinant XPA lacking these glycine residues and Phe75, which was unable to bind ERCC1 [69]. Other residues appear to be responsible for stabilization and strengthening of the XPA-ERCC1 interaction [5,68,69] (Table 1; Fig. 4).…”

Section: Preparing the Site: Xpa Structure And Post-translational Modsupporting

confidence: 94%

“…XPs include seven proteins termed XPA through XPG [1,[4][5][6]. These proteins coordinate and promote the following basic steps in the NER pathway: (i) recognition of the distortion in the DNA molecule caused by a bulky nucleotide lesion, (ii) assembly of the repair machinery (the ''preincision complex''), (iii) excision of the damaged nucleotide via dual incision, and (iv) synthesis of a new DNA fragment followed by ligation of the synthesized fragment with the pre-existing DNA molecule [6].…”

mentioning

confidence: 99%

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Overview of xeroderma pigmentosum proteins architecture, mutations and post-translational modifications

Feltes

Bonatto

2015

Mutation Research/Reviews in Mutation Research

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Section: Preparing the Site: Xpa Structure And Post-translational Modsupporting

confidence: 94%

mentioning

confidence: 99%

Overview of xeroderma pigmentosum proteins architecture, mutations and post-translational modifications

Feltes

Bonatto

2015

Mutation Research/Reviews in Mutation Research

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“…The need for further analysis of the XPA interaction with ssDNA-dsDNA junction substrates is highlighted by multiple reports supporting the interaction as the most probable DNA structure in which XPA would be presented in vivo. Indeed, the recruitment of XPF-ERCC1 complex by XPA after strand opening by TFIIH supports a model of XPA binding at or near the ssDNA-dsDNA junction in the pre-incision complex (3,9,(43)(44)(45).…”

Section: Discussionmentioning

confidence: 80%

Checkpoint Kinase ATR Promotes Nucleotide Excision Repair of UV-induced DNA Damage via Physical Interaction with Xeroderma Pigmentosum Group A

Shell

Shkriabai

et al. 2009

Journal of Biological Chemistry

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In response to DNA damage, eukaryotic cells activate a series of DNA damage-dependent pathways that serve to arrest cell cycle progression and remove DNA damage. Coordination of cell cycle arrest and damage repair is critical for maintenance of genomic stability. However, this process is still poorly understood. Nucleotide excision repair (NER) and the ATR-dependent cell cycle checkpoint are the major pathways responsible for repair of UV-induced DNA damage. Here we show that ATR physically interacts with the NER factor Xeroderma pigmentosum group A (XPA). Using a mass spectrometry-based protein footprinting method, we found that ATR interacts with a helixturn-helix motif in the minimal DNA-binding domain of XPA where an ATR phosphorylation site (serine 196) is located. XPAdeficient cells complemented with XPA containing a point mutation of S196A displayed a reduced repair efficiency of cyclobutane pyrimidine dimers as compared with cells complemented with wild-type XPA, although no effect was observed for repair of (6-4) photoproducts. This suggests that the ATR-dependent phosphorylation of XPA may promote NER repair of persistent DNA damage. In addition, a K188A point mutation of XPA that disrupts the ATR-XPA interaction inhibits the nuclear import of XPA after UV irradiation and, thus, significantly reduced DNA repair efficiency. By contrast, the S196A mutation has no effect on XPA nuclear translocation. Taken together, our results suggest that the ATR-XPA interaction mediated by the helix-turn-helix motif of XPA plays an important role in DNA-damage responses to promote cell survival and genomic stability after UV irradiation.

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“…During NER, the XPF endonuclease is recruited to the DNA by the XPA protein, encoded by rhp14 + in fission yeast (Hohl et al 2001;Croteau et al 2008). Similar to rad16-249, we observed fragments in MI and MII divisions in rhp14Δ ( Figure 1, B-D and File S3), suggesting that XPA and XPF also act together during meiosis.…”

Section: Xpf Required For Meiosis and Genome Stability 1459mentioning

confidence: 99%

“…However, in that case, all the spores were inviable, consistent with a catastrophic failure of DNA repair (Catlett and Forsburg 2003). We investigated the formation of fragments in other mutants.During NER, the XPF endonuclease is recruited to the DNA by the XPA protein, encoded by rhp14 + in fission yeast (Hohl et al 2001;Croteau et al 2008). Similar to rad16-249, we observed fragments in MI and MII divisions in rhp14Δ ( Figure 1, B-D and File S3), suggesting that XPA and XPF also act together during meiosis.…”

mentioning

confidence: 99%

Increased Meiotic Crossovers and Reduced Genome Stability in Absence of Schizosaccharomyces pombe Rad16 (XPF)

Mastro¹,

Forsburg

2014

Genetics

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Schizosaccharomyces pombe Rad16 is the ortholog of the XPF structure-specific endonuclease, which is required for nucleotide excision repair and implicated in the single strand annealing mechanism of recombination. We show that Rad16 is important for proper completion of meiosis. In its absence, cells suffer reduced spore viability and abnormal chromosome segregation with evidence for fragmentation. Recombination between homologous chromosomes is increased, while recombination within sister chromatids is reduced, suggesting that Rad16 is not required for typical homolog crossovers but influences the balance of recombination between the homolog and the sister. In vegetative cells, rad16 mutants show evidence for genome instability. Similar phenotypes are associated with mutants affecting Rhp14 XPA but are independent of other nucleotide excision repair proteins such as Rad13 XPG . Thus, the XPF/XPA module of the nucleotide excision repair pathway is incorporated into multiple aspects of genome maintenance even in the absence of external DNA damage.T HE XPF/ERCC1 protein complex is one of several structurespecific endonucleases that function broadly as resolvases in the repair of damaged DNA (Schwartz and Heyer 2011). Rad16/Swi9 is the fission yeast ortholog of endonuclease XPF, which forms a complex with Swi10/Rad23 (ERCC1) (Carr et al. 1994). XPF has a conserved role in nucleotide excision repair (NER) to remove UV-induced lesions in the DNA (Camenisch et al. 2006;Gregg et al. 2011). In humans, mutation of XPF is associated with xeroderma pigmentosum (XP), which causes sun sensitivity and high rates of skin cancer, as well as premature aging and neurological disorders (Camenisch et al. 2006;Gregg et al. 2011). Recent studies suggest XPF mutations are also associated with Fanconi anemia (FA), which requires repair of interstrand crosslinks (ICLs) (Bogliolo et al. 2013;Kashiyama et al. 2013). The canonical model for NER suggests that upon recognition of helix-distorting lesions, the DNA is unwound to form a bubble around the damage. XPA (SpRhp14) loads XPF (SpRad16) and ERCC1 (SpSwi10); XPF cleaves at the 59 end of the bubble while XPG (SpRad13), another endonuclease, cleaves at the 39 end to remove the offending segment (Fagbemi et al. 2011;Schwartz and Heyer 2011). Thus, Schizosaccharomyces pombe rad16 mutants show a decrease in (6-4) photoproduct excision (McCready et al. 1993;Carr et al. 1994).Consistent with these clinical effects, XPF is implicated in multiple mechanisms of genome maintenance (Paques and Haber 1997;Gregg et al. 2011;Schwartz and Heyer 2011). XPF is required for single strand annealing (SSA), a form of double strand break (DSB) repair distinct from typical homologous recombination (HR) (Ma et al. 2003;Kass and Jasin 2010). This occurs when short regions of homology exposed by resection are able to pair, leaving nonhomologous 39 overhangs as substrates for XPF cleavage. In budding yeast, recruitment of ScRad1 XPF and ScRad10 ERCC1 in this pathway depends on interactions with other pro...

show abstract

DNA repair gets physical: Mapping an XPA-binding site on ERCC1

Cited by 26 publications

References 48 publications

Overview of xeroderma pigmentosum proteins architecture, mutations and post-translational modifications

Overview of xeroderma pigmentosum proteins architecture, mutations and post-translational modifications

Checkpoint Kinase ATR Promotes Nucleotide Excision Repair of UV-induced DNA Damage via Physical Interaction with Xeroderma Pigmentosum Group A

Increased Meiotic Crossovers and Reduced Genome Stability in Absence of Schizosaccharomyces pombe Rad16 (XPF)

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