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  1. Article: The TRESLIN-MTBP complex couples completion of DNA replication with S/G2 transition

    Zonderland, Gijs / Vanzo, Riccardo / Amitash, Sampath / Martín-Doncel, Elena / Coscia, Fabian / Mund, Andreas / Lerdrup, Mads / Benada, Jan / Boos, Dominik / Toledo, Luis

    Molecular cell. 2022 Sept. 15, v. 82, no. 18

    2022  

    Abstract: It has been proposed that ATR kinase senses the completion of DNA replication to initiate the S/G2 transition. In contrast to this model, we show here that the TRESLIN-MTBP complex prevents a premature entry into G2 from early S-phase independently of ... ...

    Abstract It has been proposed that ATR kinase senses the completion of DNA replication to initiate the S/G2 transition. In contrast to this model, we show here that the TRESLIN-MTBP complex prevents a premature entry into G2 from early S-phase independently of ATR/CHK1 kinases. TRESLIN-MTBP acts transiently at pre-replication complexes (preRCs) to initiate origin firing and is released after the subsequent recruitment of CDC45. This dynamic behavior of TRESLIN-MTBP implements a monitoring system that checks the activation of replication forks and senses the rate of origin firing to prevent the entry into G2. This system detects the decline in the number of origins of replication that naturally occurs in very late S, which is the signature that cells use to determine the completion of DNA replication and permit the S/G2 transition. Our work introduces TRESLIN-MTBP as a key player in cell-cycle control independent of canonical checkpoints.
    Keywords DNA replication ; cell cycle ; models ; phosphotransferases (kinases)
    Language English
    Dates of publication 2022-0915
    Size p. 3350-3365.e7.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2022.08.006
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: The TRESLIN-MTBP complex couples completion of DNA replication with S/G2 transition.

    Zonderland, Gijs / Vanzo, Riccardo / Amitash, Sampath / Martín-Doncel, Elena / Coscia, Fabian / Mund, Andreas / Lerdrup, Mads / Benada, Jan / Boos, Dominik / Toledo, Luis

    Molecular cell

    2022  Volume 82, Issue 18, Page(s) 3350–3365.e7

    Abstract: It has been proposed that ATR kinase senses the completion of DNA replication to initiate the S/G2 transition. In contrast to this model, we show here that the TRESLIN-MTBP complex prevents a premature entry into G2 from early S-phase independently of ... ...

    Abstract It has been proposed that ATR kinase senses the completion of DNA replication to initiate the S/G2 transition. In contrast to this model, we show here that the TRESLIN-MTBP complex prevents a premature entry into G2 from early S-phase independently of ATR/CHK1 kinases. TRESLIN-MTBP acts transiently at pre-replication complexes (preRCs) to initiate origin firing and is released after the subsequent recruitment of CDC45. This dynamic behavior of TRESLIN-MTBP implements a monitoring system that checks the activation of replication forks and senses the rate of origin firing to prevent the entry into G2. This system detects the decline in the number of origins of replication that naturally occurs in very late S, which is the signature that cells use to determine the completion of DNA replication and permit the S/G2 transition. Our work introduces TRESLIN-MTBP as a key player in cell-cycle control independent of canonical checkpoints.
    MeSH term(s) Carrier Proteins/metabolism ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Checkpoint Kinase 1/genetics ; DNA Replication ; DNA-Binding Proteins/genetics
    Chemical Substances Carrier Proteins ; Cell Cycle Proteins ; DNA-Binding Proteins ; Checkpoint Kinase 1 (EC 2.7.11.1)
    Language English
    Publishing date 2022-08-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2022.08.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Physiological Tolerance to ssDNA Enables Strand Uncoupling during DNA Replication.

    Ercilla, Amaia / Benada, Jan / Amitash, Sampath / Zonderland, Gijs / Baldi, Giorgio / Somyajit, Kumar / Ochs, Fena / Costanzo, Vincenzo / Lukas, Jiri / Toledo, Luis

    Cell reports

    2020  Volume 30, Issue 7, Page(s) 2416–2429.e7

    Abstract: It has been long assumed that normally leading strand synthesis must proceed coordinated with the lagging strand to prevent strand uncoupling and the pathological accumulation of single-stranded DNA (ssDNA) in the cell, a dogma recently challenged by in ... ...

    Abstract It has been long assumed that normally leading strand synthesis must proceed coordinated with the lagging strand to prevent strand uncoupling and the pathological accumulation of single-stranded DNA (ssDNA) in the cell, a dogma recently challenged by in vitro studies in prokaryotes. Here, we report that human DNA polymerases can function independently at each strand in vivo and that the resulting strand uncoupling is supported physiologically by a cellular tolerance to ssDNA. Active forks rapidly accumulate ssDNA at the lagging strand when POLA1 is inhibited without triggering a stress response, despite ssDNA formation being considered a hallmark of replication stress. Acute POLA1 inhibition causes a lethal RPA exhaustion, but cells can duplicate their DNA with limited POLA1 activity and exacerbated strand uncoupling as long as RPA molecules suffice to protect the elevated ssDNA. Although robust, this uncoupled mode of DNA replication is also an in-built weakness that can be targeted for cancer treatment.
    MeSH term(s) DNA Replication/genetics ; DNA, Single-Stranded/genetics ; Humans ; Protein Binding/genetics
    Chemical Substances DNA, Single-Stranded
    Language English
    Publishing date 2020-02-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2020.01.067
    Database MEDical Literature Analysis and Retrieval System OnLINE

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