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Coordinated Cut and Bypass: Replication of Interstrand Crosslink-Containing DNA

Liu, Qiuzhen and Dudás, Kata and Tick, Gabriella and Haracska, Lajos (2021) Coordinated Cut and Bypass: Replication of Interstrand Crosslink-Containing DNA. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 9. pp. 1-8. ISSN 2296-634X

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Abstract

DNA interstrand crosslinks (ICLs) are covalently bound DNA lesions, which are commonly induced by chemotherapeutic drugs, such as cisplatin and mitomycin C or endogenous byproducts of metabolic processes. This type of DNA lesion can block ongoing RNA transcription and DNA replication and thus cause genome instability and cancer. Several cellular defense mechanism, such as the Fanconi anemia pathway have developed to ensure accurate repair and DNA replication when ICLs are present. Various structure-specific nucleases and translesion synthesis (TLS) polymerases have come into focus in relation to ICL bypass. Current models propose that a structure-specific nuclease incision is needed to unhook the ICL from the replication fork, followed by the activity of a low-fidelity TLS polymerase enabling replication through the unhooked ICL adduct. This review focuses on how, in parallel with the Fanconi anemia pathway, PCNA interactions and ICL-induced PCNA ubiquitylation regulate the recruitment, substrate specificity, activity, and coordinated action of certain nucleases and TLS polymerases in the execution of stalled replication fork rescue via ICL bypass.

Item Type: Article
Uncontrolled Keywords: interstrand crosslink; DNA repair; translesion synthesis polymerases; PCNA ubiquitylation; structure�specific nuclease
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH426 Genetics / genetika, örökléstan
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 21 Sep 2021 07:02
Last Modified: 25 Apr 2023 11:32
URI: http://real.mtak.hu/id/eprint/129863

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