Unknown

Dataset Information

0

Roles of human POLD1 and POLD3 in genome stability.


ABSTRACT: DNA replication is essential for cellular proliferation. If improperly controlled it can constitute a major source of genome instability, frequently associated with cancer and aging. POLD1 is the catalytic subunit and POLD3 is an accessory subunit of the replicative Pol δ polymerase, which also functions in DNA repair, as well as the translesion synthesis polymerase Pol ζ, whose catalytic subunit is REV3L. In cells depleted of POLD1 or POLD3 we found a differential but general increase in genome instability as manifested by DNA breaks, S-phase progression impairment and chromosome abnormalities. Importantly, we showed that both proteins are needed to maintain the proper amount of active replication origins and that POLD3-depletion causes anaphase bridges accumulation. In addition, POLD3-associated DNA damage showed to be dependent on RNA-DNA hybrids pointing toward an additional and specific role of this subunit in genome stability. Interestingly, a similar increase in RNA-DNA hybrids-dependent genome instability was observed in REV3L-depleted cells. Our findings demonstrate a key role of POLD1 and POLD3 in genome stability and S-phase progression revealing RNA-DNA hybrids-dependent effects for POLD3 that might be partly due to its Pol ζ interaction.

SUBMITTER: Tumini E 

PROVIDER: S-EPMC5156928 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

Roles of human POLD1 and POLD3 in genome stability.

Tumini Emanuela E   Barroso Sonia S   -Calero Carmen Pérez CP   Aguilera Andrés A  

Scientific reports 20161215


DNA replication is essential for cellular proliferation. If improperly controlled it can constitute a major source of genome instability, frequently associated with cancer and aging. POLD1 is the catalytic subunit and POLD3 is an accessory subunit of the replicative Pol δ polymerase, which also functions in DNA repair, as well as the translesion synthesis polymerase Pol ζ, whose catalytic subunit is REV3L. In cells depleted of POLD1 or POLD3 we found a differential but general increase in genome  ...[more]

Similar Datasets

| S-EPMC8883456 | biostudies-literature
| S-EPMC8747517 | biostudies-literature
| S-EPMC6283425 | biostudies-literature
| S-EPMC10047664 | biostudies-literature
| S-EPMC4053435 | biostudies-literature
| S-EPMC4471906 | biostudies-literature
| S-EPMC3804285 | biostudies-literature
| S-EPMC6990415 | biostudies-literature
| S-EPMC7873659 | biostudies-literature
| S-EPMC9117041 | biostudies-literature