Double-check Probing of DNA Bending and Unwinding by XPA-RPA: an Architectural Function in DNA Repair

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2001 Jul 4

PMID 11432842

Citations 82

Authors

M Missura

T Buterin

R Hindges

U Hubscher

J Kasparkova

V Brabec

H Naegeli

Affiliations

Soon will be listed here.

Abstract

The multiprotein factor composed of XPA and replication protein A (RPA) is an essential subunit of the mammalian nucleotide excision repair system. Although XPA-RPA has been implicated in damage recognition, its activity in the DNA repair pathway remains controversial. By replacing DNA adducts with mispaired bases or non-hybridizing analogues, we found that the weak preference of XPA and RPA for damaged substrates is entirely mediated by indirect readout of DNA helix conformations. Further screening with artificially distorted substrates revealed that XPA binds most efficiently to rigidly bent duplexes but not to single-stranded DNA. Conversely, RPA recognizes single-stranded sites but not backbone bending. Thus, the association of XPA with RPA generates a double-check sensor that detects, simultaneously, backbone and base pair distortion of DNA. The affinity of XPA for sharply bent duplexes, characteristic of architectural proteins, is not compatible with a direct function during recognition of nucleotide lesions. Instead, XPA in conjunction with RPA may constitute a regulatory factor that monitors DNA bending and unwinding to verify the damage-specific localization of repair complexes or control their correct three-dimensional assembly.

Citing Articles

Metal nanoparticles for cancer therapy: Precision targeting of DNA damage.

Chen Q, Fang C, Xia F, Wang Q, Li F, Ling D Acta Pharm Sin B. 2024; 14(3):1132-1149.

PMID: 38486992 PMC: 10934341. DOI: 10.1016/j.apsb.2023.08.031.

Melatonin improves the vitrification of sheep morulae by modulating transcriptome.

Ji P, Liu Y, Yan L, Jia Y, Zhao M, Lv D Front Vet Sci. 2023; 10:1212047.

PMID: 37920328 PMC: 10619913. DOI: 10.3389/fvets.2023.1212047.

A disease-associated XPA allele interferes with TFIIH binding and primarily affects transcription-coupled nucleotide excision repair.

van den Heuvel D, Kim M, Wondergem A, van der Meer P, Witkamp M, Lambregtse F Proc Natl Acad Sci U S A. 2023; 120(11):e2208860120.

PMID: 36893274 PMC: 10089173. DOI: 10.1073/pnas.2208860120.

The XPA Protein-Life under Precise Control.

Krasikova Y, Lavrik O, Rechkunova N Cells. 2022; 11(23).

PMID: 36496984 PMC: 9739396. DOI: 10.3390/cells11233723.

A nuclease-mimetic platinum nanozyme induces concurrent DNA platination and oxidative cleavage to overcome cancer drug resistance.

Li F, Sun H, Ren J, Zhang B, Hu X, Fang C Nat Commun. 2022; 13(1):7361.

PMID: 36450764 PMC: 9712435. DOI: 10.1038/s41467-022-35022-w.

References

Lao Y, Gomes X, Ren Y, Taylor J, Wold M . Replication protein A interactions with DNA. III. Molecular basis of recognition of damaged DNA. Biochemistry. 2000; 39(5):850-9. DOI: 10.1021/bi991704s. View

Ikegami T, Kuraoka I, Saijo M, Kodo N, Kyogoku Y, Morikawa K . Solution structure of the DNA- and RPA-binding domain of the human repair factor XPA. Nat Struct Biol. 1998; 5(8):701-6. DOI: 10.1038/1400. View

de Boer J, Hoeijmakers J . Nucleotide excision repair and human syndromes. Carcinogenesis. 2000; 21(3):453-60. DOI: 10.1093/carcin/21.3.453. View

Yokoi M, Masutani C, Maekawa T, Sugasawa K, Ohkuma Y, Hanaoka F . The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA. J Biol Chem. 2000; 275(13):9870-5. DOI: 10.1074/jbc.275.13.9870. View

Batty D, Levine A, Wood R . Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sites. J Mol Biol. 2000; 300(2):275-90. DOI: 10.1006/jmbi.2000.3857. View

Tang J, Hwang B, Ford J, HANAWALT P, Chu G . Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis. Mol Cell. 2000; 5(4):737-44. PMC: 2894271. DOI: 10.1016/s1097-2765(00)80252-x. View

MER G, Bochkarev A, Gupta R, Bochkareva E, Frappier L, Ingles C . Structural basis for the recognition of DNA repair proteins UNG2, XPA, and RAD52 by replication factor RPA. Cell. 2000; 103(3):449-56. DOI: 10.1016/s0092-8674(00)00136-7. View

Verhoeven E, Wyman C, Moolenaar G, Hoeijmakers J, Goosen N . Architecture of nucleotide excision repair complexes: DNA is wrapped by UvrB before and after damage recognition. EMBO J. 2001; 20(3):601-11. PMC: 133479. DOI: 10.1093/emboj/20.3.601. View

Hunter W, Brown T, Anand N, KENNARD O . Structure of an adenine-cytosine base pair in DNA and its implications for mismatch repair. Nature. 1986; 320(6062):552-5. DOI: 10.1038/320552a0. View

10.

de Laat W, Appeldoorn E, Sugasawa K, Weterings E, Jaspers N, Hoeijmakers J . DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair. Genes Dev. 1998; 12(16):2598-609. PMC: 317078. DOI: 10.1101/gad.12.16.2598. View

11.

Sugasawa K, Ng J, Masutani C, Iwai S, van der Spek P, Eker A . Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Mol Cell. 1998; 2(2):223-32. DOI: 10.1016/s1097-2765(00)80132-x. View

12.

Kobayashi T, Takeuchi S, Saijo M, Nakatsu Y, Morioka H, Otsuka E . Mutational analysis of a function of xeroderma pigmentosum group A (XPA) protein in strand-specific DNA repair. Nucleic Acids Res. 1998; 26(20):4662-8. PMC: 147903. DOI: 10.1093/nar/26.20.4662. View

13.

Wakasugi M, Sancar A . Order of assembly of human DNA repair excision nuclease. J Biol Chem. 1999; 274(26):18759-68. DOI: 10.1074/jbc.274.26.18759. View

14.

Fujiwara Y, Masutani C, Mizukoshi T, Kondo J, Hanaoka F, Iwai S . Characterization of DNA recognition by the human UV-damaged DNA-binding protein. J Biol Chem. 1999; 274(28):20027-33. DOI: 10.1074/jbc.274.28.20027. View

15.

Gonzalez A, Eritja R, Aymami J, Azorin F, Coll M . Crystal structure of a DNA Holliday junction. Nat Struct Biol. 1999; 6(10):913-7. DOI: 10.1038/13277. View

16.

Venema J, van Hoffen A, Karcagi V, Natarajan A, van Zeeland A, Mullenders L . Xeroderma pigmentosum complementation group C cells remove pyrimidine dimers selectively from the transcribed strand of active genes. Mol Cell Biol. 1991; 11(8):4128-34. PMC: 361228. DOI: 10.1128/mcb.11.8.4128-4134.1991. View

17.

Huang J, Svoboda D, Reardon J, Sancar A . Human nucleotide excision nuclease removes thymine dimers from DNA by incising the 22nd phosphodiester bond 5' and the 6th phosphodiester bond 3' to the photodimer. Proc Natl Acad Sci U S A. 1992; 89(8):3664-8. PMC: 48929. DOI: 10.1073/pnas.89.8.3664. View

18.

Shi Q, Thresher R, Sancar A, Griffith J . Electron microscopic study of (A)BC excinuclease. DNA is sharply bent in the UvrB-DNA complex. J Mol Biol. 1992; 226(2):425-32. DOI: 10.1016/0022-2836(92)90957-l. View

19.

Georgaki A, Strack B, Podust V, Hubscher U . DNA unwinding activity of replication protein A. FEBS Lett. 1992; 308(3):240-4. DOI: 10.1016/0014-5793(92)81283-r. View

20.

Jones C, Wood R . Preferential binding of the xeroderma pigmentosum group A complementing protein to damaged DNA. Biochemistry. 1993; 32(45):12096-104. DOI: 10.1021/bi00096a021. View