Functional roles of parp2 in assembling protein–protein complexes involved in base excision dna repair

Inna Vasil’eva, Nina Moor, Rashid Anarbaev, Mikhail Kutuzov, Olga Lavrik

Research output: Contribution to journalArticlepeer-review

Abstract

Poly(ADP‐ribose) polymerase 2 (PARP2) participates in base excision repair (BER) along-side PARP1, but its functions are still under study. Here, we characterize binding affinities of PARP2 for other BER proteins (PARP1, APE1, Polβ, and XRCC1) and oligomerization states of the homo-and hetero‐associated complexes using fluorescence‐based and light scattering techniques. To com-pare PARP2 and PARP1 in the efficiency of PAR synthesis, in the absence and presence of protein partners, the size of PARP2 PARylated in various reaction conditions was measured. Unlike PARP1, PARP2 forms more dynamic complexes with common protein partners, and their stability is effectively modulated by DNA intermediates. Apparent binding affinity constants determined for homo-and hetero‐oligomerized PARP1 and PARP2 provide evidence that the major form of PARP2 at ex-cessive PARP1 level is their heterocomplex. Autoregulation of PAR elongation at high PARP and NAD+ concentrations is stronger for PARP2 than for PARP1, and the activity of PARP2 is more effectively inhibited by XRCC1. Moreover, the activity of both PARP1 and PARP2 is suppressed upon their heteroPARylation. Taken together, our findings suggest that PARP2 can function differ-ently in BER, promoting XRCC1‐dependent repair (similarly to PARP1) or an alternative XRCC1‐ independent mechanism via hetero‐oligomerization with PARP1.

Original languageEnglish
Article number4679
JournalInternational Journal of Molecular Sciences
Volume22
Issue number9
DOIs
Publication statusPublished - 1 May 2021

Keywords

  • Base excision repair
  • Dynamic light scattering
  • Fluorescence techniques
  • PARP1
  • PARP2
  • Poly(ADP‐ribosyl)ation
  • Protein–protein interaction

OECD FOS+WOS

  • 1.02 COMPUTER AND INFORMATION SCIENCES
  • 1.04 CHEMICAL SCIENCES
  • 2.04 CHEMICAL ENGINEERING
  • 1.06 BIOLOGICAL SCIENCES

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