Artículo
Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability
Mansilla, Sabrina Florencia
; Bertolin, Agostina P.; Venerus Arbilla, Sofía
; Castaño, Bryan Alain Alexis; Jahjah, Tiya; Singh, Jenny K.; Siri, Sebastian Omar
; Castro, María Victoria; de la Vega Páez, María Belén
; Quinet, Annabel; Wiesmüller, Lisa; Gottifredi, Vanesa
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Fecha de publicación:
04/2023
Editorial:
Science Advances is the American Association for the Advancement of Science
Revista:
Science Advances
ISSN:
2375-2548
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Recent studies have described a DNA damage tolerance pathway choice that involves a competition between PrimPol-mediated repriming and fork reversal. Screening different translesion DNA synthesis (TLS) polymerases by the use of tools for their depletion, we identified a unique role of Pol ι in regulating such a pathway choice. Pol ι deficiency unleashes PrimPol-dependent repriming, which accelerates DNA replication in a pathway that is epistatic with ZRANB3 knockdown. In Pol ι–depleted cells, the excess participation of PrimPol in nascent DNA elongation reduces replication stress signals, but thereby also checkpoint activation in S phase, triggering chromosome instability in M phase. This TLS-independent function of Pol ι requires its PCNA-interacting but not its polymerase domain. Our findings unravel an unanticipated role of Pol ι in protecting the genome stability of cells from detrimental changes in DNA replication dynamics caused by PrimPol.
Palabras clave:
Pol iota
,
DNA Replication
,
Gaps
,
PrimPol
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Articulos(IIBBA)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Citación
Mansilla, Sabrina Florencia; Bertolin, Agostina P.; Venerus Arbilla, Sofía; Castaño, Bryan Alain Alexis; Jahjah, Tiya; et al.; Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability; Science Advances is the American Association for the Advancement of Science; Science Advances; 9; 15; 4-2023; 1-19
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