Protein Dynamics in Complex DNA Lesions

被引：112

作者：

Aleksandrov, Radoslav ^{[1
]}

Dotchev, Anton ^{[1
]}

Poser, Ina ^{[2
]}

Krastev, Dragomir ^{[2
,6
]}

Georgiev, Georgi ^{[3
]}

Panova, Greta ^{[4
]}

Babukov, Yordan ^{[1
,3
]}

Danovski, Georgi ^{[1
]}

Dyankova, Teodora ^{[1
]}

Hubatsch, Lars ^{[2
]}

Ivanova, Aneliya ^{[1
]}

Atemin, Aleksandar ^{[1
]}

Nedelcheva-Veleva, Marina N. ^{[1
]}

Hasse, Susanne ^{[2
]}

Sarov, Mihail ^{[2
]}

Buchholz, Frank ^{[2
,5
]}

Hyman, Anthony A. ^{[2
]}

Grill, Stephan W. ^{[2
,7
]}

Stoynov, Stoyno S. ^{[1
]}

机构：

[1] Bulgarian Acad Sci, Inst Mol Biol, Acad G Bonchev Str Bl 21, BU-1113 Sofia, Bulgaria

[2] Max Planck Inst Mol Cell Biol & Genet, 108 Pfotenhauerstr, D-01307 Dresden, Germany

[3] Sofia Univ, Fac Math & Informat, 5 James Bourchier Blvd, Sofia 1164, Bulgaria

[4] Univ Penn, Dept Math, 209 South 33rd St, Philadelphia, PA 19104 USA

[5] Tech Univ Dresden, UCC, Med Fac Carl Gustav Carus, Med Syst Biol, Fetscherstr 74, D-01307 Dresden, Germany

[6] Inst Canc Res, London SW3 6JB, England

[7] Tech Univ, Biotechnol Ctr, 47-49 Tatzberg, D-01307 Dresden, Germany

来源：

MOLECULAR CELL | 2018年 / 69卷 / 06期

基金：

欧洲研究理事会;

关键词：

NUCLEOTIDE EXCISION-REPAIR; DOUBLE-STRAND BREAK; HOMOLOGOUS RECOMBINATION REPAIR; IN-VIVO; DAMAGE SITES; HUMAN-CELLS; END RESECTION; PCNA; REPLICATION; RECRUITMENT;

D O I：

10.1016/j.molcel.2018.02.016

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：

A single mutagen can generate multiple different types of DNA lesions. How different repair pathways cooperate in complex DNA lesions, however, remains largely unclear. Here we measured, clustered, and modeled the kinetics of recruitment and dissociation of 70 DNA repair proteins to laser-induced DNA damage sites in HeLa cells. The precise timescale of protein recruitment reveals that error-prone translesion polymerases are considerably delayed compared to error-free polymerases. We show that this is ensured by the delayed recruitment of RAD18 to double-strand break sites. The time benefit of error-free polymerases disappears when PARP inhibition significantly delays PCNA recruitment. Moreover, removal of PCNA from complex DNA damage sites correlates with RPA loading during 5'-DNA end resection. Our systematic study of the dynamics of DNA repair proteins in complex DNA lesions reveals the multifaceted coordination between the repair pathways and provides a kinetics-based resource to study genomic instability and anticancer drug impact.

引用

页码：1046 / +

页数：21

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