RIF1 Links Replication Timing with Fork Reactivation and DNA Double-Strand Break Repair

Replication timing (RT) is a cellular program to coordinate initiation of DNA replication in all origins within the genome. RIF1 (replication timing regulatory factor 1) is a master regulator of RT in human cells. This role of RIF1 is associated with binding G4-quadruplexes and changes in 3D chromat...

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Autores principales:	Janusz Blasiak, Joanna Szczepańska, Anna Sobczuk, Michal Fila, Elzbieta Pawlowska
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	RIF1 replication timing DNA double-strand break repair reactivation of replication fork TP53BP1 BRCA1 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/b2a85a44d92d472fa1e093dd9c039dc1
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spelling	oai:doaj.org-article:b2a85a44d92d472fa1e093dd9c039dc12021-11-11T16:54:20ZRIF1 Links Replication Timing with Fork Reactivation and DNA Double-Strand Break Repair10.3390/ijms2221114401422-00671661-6596https://doaj.org/article/b2a85a44d92d472fa1e093dd9c039dc12021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11440https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Replication timing (RT) is a cellular program to coordinate initiation of DNA replication in all origins within the genome. RIF1 (replication timing regulatory factor 1) is a master regulator of RT in human cells. This role of RIF1 is associated with binding G4-quadruplexes and changes in 3D chromatin that may suppress origin activation over a long distance. Many effects of RIF1 in fork reactivation and DNA double-strand (DSB) repair (DSBR) are underlined by its interaction with TP53BP1 (tumor protein p53 binding protein). In G1, RIF1 acts antagonistically to BRCA1 (BRCA1 DNA repair associated), suppressing end resection and homologous recombination repair (HRR) and promoting non-homologous end joining (NHEJ), contributing to DSBR pathway choice. RIF1 is an important element of intra-S-checkpoints to recover damaged replication fork with the involvement of HRR. High-resolution microscopic studies show that RIF1 cooperates with TP53BP1 to preserve 3D structure and epigenetic markers of genomic loci disrupted by DSBs. Apart from TP53BP1, RIF1 interact with many other proteins, including proteins involved in DNA damage response, cell cycle regulation, and chromatin remodeling. As impaired RT, DSBR and fork reactivation are associated with genomic instability, a hallmark of malignant transformation, RIF1 has a diagnostic, prognostic, and therapeutic potential in cancer. Further studies may reveal other aspects of common regulation of RT, DSBR, and fork reactivation by RIF1.Janusz BlasiakJoanna SzczepańskaAnna SobczukMichal FilaElzbieta PawlowskaMDPI AGarticleRIF1replication timingDNA double-strand break repairreactivation of replication forkTP53BP1BRCA1Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11440, p 11440 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	RIF1 replication timing DNA double-strand break repair reactivation of replication fork TP53BP1 BRCA1 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	RIF1 replication timing DNA double-strand break repair reactivation of replication fork TP53BP1 BRCA1 Biology (General) QH301-705.5 Chemistry QD1-999 Janusz Blasiak Joanna Szczepańska Anna Sobczuk Michal Fila Elzbieta Pawlowska RIF1 Links Replication Timing with Fork Reactivation and DNA Double-Strand Break Repair
description	Replication timing (RT) is a cellular program to coordinate initiation of DNA replication in all origins within the genome. RIF1 (replication timing regulatory factor 1) is a master regulator of RT in human cells. This role of RIF1 is associated with binding G4-quadruplexes and changes in 3D chromatin that may suppress origin activation over a long distance. Many effects of RIF1 in fork reactivation and DNA double-strand (DSB) repair (DSBR) are underlined by its interaction with TP53BP1 (tumor protein p53 binding protein). In G1, RIF1 acts antagonistically to BRCA1 (BRCA1 DNA repair associated), suppressing end resection and homologous recombination repair (HRR) and promoting non-homologous end joining (NHEJ), contributing to DSBR pathway choice. RIF1 is an important element of intra-S-checkpoints to recover damaged replication fork with the involvement of HRR. High-resolution microscopic studies show that RIF1 cooperates with TP53BP1 to preserve 3D structure and epigenetic markers of genomic loci disrupted by DSBs. Apart from TP53BP1, RIF1 interact with many other proteins, including proteins involved in DNA damage response, cell cycle regulation, and chromatin remodeling. As impaired RT, DSBR and fork reactivation are associated with genomic instability, a hallmark of malignant transformation, RIF1 has a diagnostic, prognostic, and therapeutic potential in cancer. Further studies may reveal other aspects of common regulation of RT, DSBR, and fork reactivation by RIF1.
format	article
author	Janusz Blasiak Joanna Szczepańska Anna Sobczuk Michal Fila Elzbieta Pawlowska
author_facet	Janusz Blasiak Joanna Szczepańska Anna Sobczuk Michal Fila Elzbieta Pawlowska
author_sort	Janusz Blasiak
title	RIF1 Links Replication Timing with Fork Reactivation and DNA Double-Strand Break Repair
title_short	RIF1 Links Replication Timing with Fork Reactivation and DNA Double-Strand Break Repair
title_full	RIF1 Links Replication Timing with Fork Reactivation and DNA Double-Strand Break Repair
title_fullStr	RIF1 Links Replication Timing with Fork Reactivation and DNA Double-Strand Break Repair
title_full_unstemmed	RIF1 Links Replication Timing with Fork Reactivation and DNA Double-Strand Break Repair
title_sort	rif1 links replication timing with fork reactivation and dna double-strand break repair
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b2a85a44d92d472fa1e093dd9c039dc1
work_keys_str_mv	AT januszblasiak rif1linksreplicationtimingwithforkreactivationanddnadoublestrandbreakrepair AT joannaszczepanska rif1linksreplicationtimingwithforkreactivationanddnadoublestrandbreakrepair AT annasobczuk rif1linksreplicationtimingwithforkreactivationanddnadoublestrandbreakrepair AT michalfila rif1linksreplicationtimingwithforkreactivationanddnadoublestrandbreakrepair AT elzbietapawlowska rif1linksreplicationtimingwithforkreactivationanddnadoublestrandbreakrepair
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RIF1 Links Replication Timing with Fork Reactivation and DNA Double-Strand Break Repair

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