Research output: Contribution to journal › Article › peer-review
Replication protein A as a modulator of the poly(ADP-ribose)polymerase 1 activity. / Maltseva, Ekaterina A.; Krasikova, Yulia S.; Sukhanova, Maria V. et al.
In: DNA Repair, Vol. 72, 01.12.2018, p. 28-38.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Replication protein A as a modulator of the poly(ADP-ribose)polymerase 1 activity
AU - Maltseva, Ekaterina A.
AU - Krasikova, Yulia S.
AU - Sukhanova, Maria V.
AU - Rechkunova, Nadejda I.
AU - Lavrik, Olga I.
N1 - Publisher Copyright: © 2018 Elsevier B.V.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Replication protein A contributes to all major pathways of DNA metabolism and is a target for post-translation modifications, including poly(ADP-ribosyl)ation catalyzed by PARP1. Here we demonstrate that the efficiency of RPA poly(ADP-ribosyl)ation strongly depends on the structure of DNA used for PARP1 activation and on the polarity of RPA binding. Moreover, RPA influences PARP1 activity, and this effect also depends on DNA structure: RPA inhibits PAR synthesis catalyzed by PARP1 in the presence of ssDNA and stimulates it in the presence of a DNA duplex, in particular that containing a nick or a gap. Using fluorescently labeled proteins, we showed their direct interaction and characterized it quantitatively. RPA can accelerate the replacement of poly(ADP-ribosyl)ated PARP1 molecules bound to DNA by the unmodified ones. Thus, our data allow us to suggest that the balance between the affinities of PARP1 and RPA for DNA and the interaction of these proteins with each other are the cornerstone of the modulating effect of RPA on PARP1 activity. This effect might contribute to the regulation of PARP1 activity in various DNA processing mechanisms including DNA replication and repair pathways, where both PARP1 and RPA participate.
AB - Replication protein A contributes to all major pathways of DNA metabolism and is a target for post-translation modifications, including poly(ADP-ribosyl)ation catalyzed by PARP1. Here we demonstrate that the efficiency of RPA poly(ADP-ribosyl)ation strongly depends on the structure of DNA used for PARP1 activation and on the polarity of RPA binding. Moreover, RPA influences PARP1 activity, and this effect also depends on DNA structure: RPA inhibits PAR synthesis catalyzed by PARP1 in the presence of ssDNA and stimulates it in the presence of a DNA duplex, in particular that containing a nick or a gap. Using fluorescently labeled proteins, we showed their direct interaction and characterized it quantitatively. RPA can accelerate the replacement of poly(ADP-ribosyl)ated PARP1 molecules bound to DNA by the unmodified ones. Thus, our data allow us to suggest that the balance between the affinities of PARP1 and RPA for DNA and the interaction of these proteins with each other are the cornerstone of the modulating effect of RPA on PARP1 activity. This effect might contribute to the regulation of PARP1 activity in various DNA processing mechanisms including DNA replication and repair pathways, where both PARP1 and RPA participate.
KW - PARP1
KW - Poly(ADP-ribosyl)ation
KW - Protein–protein interaction
KW - RPA
KW - POLARITY
KW - DNA
KW - POLYMERASE
KW - EXCISION
KW - STRESS
KW - BINDING
KW - STRAND
KW - Protein protein interaction
KW - DNA/metabolism
KW - Poly Adenosine Diphosphate Ribose/metabolism
KW - Biocatalysis
KW - Humans
KW - Replication Protein A/metabolism
KW - Poly (ADP-Ribose) Polymerase-1/metabolism
KW - Protein Processing, Post-Translational
UR - http://www.scopus.com/inward/record.url?scp=85054149315&partnerID=8YFLogxK
U2 - 10.1016/j.dnarep.2018.09.010
DO - 10.1016/j.dnarep.2018.09.010
M3 - Article
C2 - 30291044
AN - SCOPUS:85054149315
VL - 72
SP - 28
EP - 38
JO - DNA Repair
JF - DNA Repair
SN - 1568-7864
ER -
ID: 16947837