RNA-guided DNA base damage repair via DNA polymerase-mediated nick translation

被引：2

作者：

Tsegay, Pawlos S. ^{[1
]}

Hernandez, Daniela ^{[2
]}

Qu, Fei ^{[1
]}

Olatunji, Mustapha ^{[1
]}

Mamun, Yasir ^{[1
]}

Chapagain, Prem ^{[3
,4
]}

Liu, Yuan ^{[1
,2
,4
]}

机构：

[1] Florida Int Univ, Biochem PhD Program, Miami, FL 33199 USA

[2] Florida Int Univ, Dept Chem & Biochem, Miami, FL 33199 USA

[3] Florida Int Univ, Dept Phys, Miami, FL 33199 USA

[4] Florida Int Univ, Biomol Sci Inst, Miami, FL 33199 USA

来源：

NUCLEIC ACIDS RESEARCH | 2023年 / 51卷 / 01期

关键词：

MOLECULAR-DYNAMICS; HOMOLOGOUS RECOMBINATION; MECHANISM; PROTEIN; SIMULATIONS; BYPASS; CHARMM; DROSHA; DICER; BETA;

D O I：

10.1093/nar/gkac1178

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

DNA repair is mediated by DNA synthesis guided by a DNA template. Recent studies have shown that DNA repair can also be accomplished by RNA-guided DNA synthesis. However, it remains unknown how RNA can guide DNA synthesis to repair DNA damage. In this study, we revealed the molecular mechanisms underlying RNA-guided DNA synthesis and base damage repair mediated by human repair DNA polymerases. We showed that pol beta, pol kappa, and pol iota predominantly synthesized one nucleotide, and pol eta, pol nu, and pol theta synthesized multi-nucleotides during RNA-guided DNA base damage repair. The steady-state kinetics showed that pol eta exhibited more efficient RNA-guided DNA synthesis than pol beta. Using molecular dynamics simulation, we further revealed dynamic conformational changes of pol beta and pol eta and their structural basis to accommodate the RNA template and misoriented triphosphates of an incoming nucleotide. We demonstrated that RNA-guided base damage repair could be accomplished by the RNA-guided DNA strand-displacement synthesis and nick translation leading to nick ligation in a double-strand DNA region. Our study revealed a novel RNA-guided base damage repair pathway during transcription and DNA replication.

引用

页码：166 / 181

页数：16

共 50 条

[41] Synthesis and Polymerase-Mediated Bypass Studies of the N2-Deoxyguanosine DNA Damage Caused by a Lucidin Analogue
Ghodke, Pratibha P.
Harikrishna, S.
Pradeepkumar, P. I.
JOURNAL OF ORGANIC CHEMISTRY, 2015, 80 (04): : 2128 - 2138
[42] DNA polymerase β outperforms DNA polymerase γ in key mitochondrial base excision repair activities
Baptiste, Beverly A.
Baringer, Stephanie L.
Kulikowicz, Tomasz
Sommers, Joshua A.
Croteau, Deborah L.
Brosh, Robert M., Jr.
Bohr, Vilhelm A.
DNA REPAIR, 2021, 99
[43] Repair of clustered damage and DNA polymerase iota
Belousova, E. A.
Lavrik, O. I.
BIOCHEMISTRY-MOSCOW, 2015, 80 (08) : 1010 - 1018
[44] RNA polymerase at the cross roads of DNA repair
Grossman, L
Ahn, B
Lin, G
Kovalsky, O
FASEB JOURNAL, 1997, 11 (09): : A1013 - A1013
[45] Repair of clustered damage and DNA polymerase iota
E. A. Belousova
O. I. Lavrik
Biochemistry (Moscow), 2015, 80 : 1010 - 1018
[46] Rational regulation of DNA polymerase-mediated mutagenesis and autonomous 3′-5′-exonucleases
Krutyakov, VM
MOLECULAR BIOLOGY, 1998, 32 (02) : 197 - 199
[47] DNA-POLYMERASE-DELTA IS REQUIRED FOR BASE EXCISION-REPAIR OF DNA METHYLATION DAMAGE IN SACCHAROMYCES CERVISIAE
BLANK, A
KIM, B
LOEB, LA
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (19) : 9047 - 9051
[48] Transposon-associated TnpB is a programmable RNA-guided DNA endonuclease
Karvelis, Tautvydas
Druteika, Gytis
Bigelyte, Greta
Budre, Karolina
Zedaveinyte, Rimante
Silanskas, Arunas
Kazlauskas, Darius
Venclovas, Ceslovas
Siksnys, Virginijus
NATURE, 2021, 599 (7886) : 692 - +
[49] DNA interrogation by the CRISPR RNA-guided endonuclease Cas9
Sternberg, Samuel H.
Redding, Sy
Jinek, Martin
Greene, Eric C.
Doudna, Jennifer A.
NATURE, 2014, 507 (7490) : 62 - +
[50] Complexities of the DNA base excision repair pathway for repair of oxidative DNA damage
Mitra, S
Boldogh, I
Izumi, T
Hazra, TK
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, 2001, 38 (2-3) : 180 - 190

← 1 2 3 4 5 →