Activation of the DNA-repair mechanism through NBS1 and MRE11 diffusion

Ida Friis*, Ilia A. Solov’yov

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

95 Downloads (Pure)

Resumé

The non-homologous end joining of a DNA double strand break is initiated by the MRE11-NBS1-RAD50 complex whose subunits are the first three proteins to arrive to the breakage site thereby making the recruitment time of MRE11, NBS1 and RAD50 essential for cell survival. In the present investigation, the nature of MRE11 and NBS1 transportation from the cytoplasm to the nucleus, hosting the damaged DNA strand, is hypothesized to be a passive diffusive process. The feasibility of such a mechanism is addressed through theoretical and computational approaches which permit establishing the characteristic recruitment time of MRE11 and NBS1 by the nucleus. A computational model of a cell is constructed from a set of biological parameters and the kinetic Monte Carlo algorithm is used to simulate the diffusing MRE11 and NBS1 particles as a random walk process. To accurately describe the experimented data, it is discovered that MRE11 and NBS1 should start diffusion from significantly different starting positions which suggests that diffusion might not be the only transport mechanism of repair protein recruitment to the DNA break.

OriginalsprogEngelsk
Artikelnummere1006362
TidsskriftPloS Computational Biology
Vol/bind14
Udgave nummer7
Antal sider16
ISSN1553-734X
DOI
StatusUdgivet - 1. jul. 2018

Fingeraftryk

DNA repair
repair
Repair
Activation
DNA
DNA End-Joining Repair
Chemical activation
Nucleus
Proteins
Protein
Kinetic Monte Carlo
Cell Survival
protein
Breakage
Monte Carlo Algorithm
Cell
cytoplasm
breakage
Random processes
Joining

Citer dette

@article{aeec801ffc8247469c13b55d76e57efc,
title = "Activation of the DNA-repair mechanism through NBS1 and MRE11 diffusion",
abstract = "The non-homologous end joining of a DNA double strand break is initiated by the MRE11-NBS1-RAD50 complex whose subunits are the first three proteins to arrive to the breakage site thereby making the recruitment time of MRE11, NBS1 and RAD50 essential for cell survival. In the present investigation, the nature of MRE11 and NBS1 transportation from the cytoplasm to the nucleus, hosting the damaged DNA strand, is hypothesized to be a passive diffusive process. The feasibility of such a mechanism is addressed through theoretical and computational approaches which permit establishing the characteristic recruitment time of MRE11 and NBS1 by the nucleus. A computational model of a cell is constructed from a set of biological parameters and the kinetic Monte Carlo algorithm is used to simulate the diffusing MRE11 and NBS1 particles as a random walk process. To accurately describe the experimented data, it is discovered that MRE11 and NBS1 should start diffusion from significantly different starting positions which suggests that diffusion might not be the only transport mechanism of repair protein recruitment to the DNA break.",
author = "Ida Friis and Solov’yov, {Ilia A.}",
year = "2018",
month = "7",
day = "1",
doi = "10.1371/journal.pcbi.1006362",
language = "English",
volume = "14",
journal = "PLoS Computational Biology",
issn = "1553-734X",
publisher = "Public Library of Science",
number = "7",

}

Activation of the DNA-repair mechanism through NBS1 and MRE11 diffusion. / Friis, Ida; Solov’yov, Ilia A.

I: PloS Computational Biology, Bind 14, Nr. 7, e1006362, 01.07.2018.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Activation of the DNA-repair mechanism through NBS1 and MRE11 diffusion

AU - Friis, Ida

AU - Solov’yov, Ilia A.

PY - 2018/7/1

Y1 - 2018/7/1

N2 - The non-homologous end joining of a DNA double strand break is initiated by the MRE11-NBS1-RAD50 complex whose subunits are the first three proteins to arrive to the breakage site thereby making the recruitment time of MRE11, NBS1 and RAD50 essential for cell survival. In the present investigation, the nature of MRE11 and NBS1 transportation from the cytoplasm to the nucleus, hosting the damaged DNA strand, is hypothesized to be a passive diffusive process. The feasibility of such a mechanism is addressed through theoretical and computational approaches which permit establishing the characteristic recruitment time of MRE11 and NBS1 by the nucleus. A computational model of a cell is constructed from a set of biological parameters and the kinetic Monte Carlo algorithm is used to simulate the diffusing MRE11 and NBS1 particles as a random walk process. To accurately describe the experimented data, it is discovered that MRE11 and NBS1 should start diffusion from significantly different starting positions which suggests that diffusion might not be the only transport mechanism of repair protein recruitment to the DNA break.

AB - The non-homologous end joining of a DNA double strand break is initiated by the MRE11-NBS1-RAD50 complex whose subunits are the first three proteins to arrive to the breakage site thereby making the recruitment time of MRE11, NBS1 and RAD50 essential for cell survival. In the present investigation, the nature of MRE11 and NBS1 transportation from the cytoplasm to the nucleus, hosting the damaged DNA strand, is hypothesized to be a passive diffusive process. The feasibility of such a mechanism is addressed through theoretical and computational approaches which permit establishing the characteristic recruitment time of MRE11 and NBS1 by the nucleus. A computational model of a cell is constructed from a set of biological parameters and the kinetic Monte Carlo algorithm is used to simulate the diffusing MRE11 and NBS1 particles as a random walk process. To accurately describe the experimented data, it is discovered that MRE11 and NBS1 should start diffusion from significantly different starting positions which suggests that diffusion might not be the only transport mechanism of repair protein recruitment to the DNA break.

U2 - 10.1371/journal.pcbi.1006362

DO - 10.1371/journal.pcbi.1006362

M3 - Journal article

VL - 14

JO - PLoS Computational Biology

JF - PLoS Computational Biology

SN - 1553-734X

IS - 7

M1 - e1006362

ER -