---
res:
  bibo_abstract:
  - Constitutional heterozygous pathogenic variants in the exonuclease domain of POLE
    and POLD1, which affect the proofreading activity of the corresponding polymerases,
    cause a cancer predisposition syndrome characterized by increased risk of gastrointestinal
    polyposis, colorectal cancer, endometrial cancer and other tumor types. The generally
    accepted explanation for the connection between the disruption of the proofreading
    activity of polymerases epsilon and delta and cancer development is through an
    increase in the somatic mutation rate. Here we studied an extended family with
    multiple members heterozygous for the pathogenic POLD1 variant c.1421T>C p.(Leu474Pro),
    which segregates with the polyposis and cancer phenotypes. Through the analysis
    of mutational patterns of patient-derived fibroblasts colonies and de novo mutations
    obtained by parent-offspring comparisons, we concluded that heterozygous POLD1
    L474P just subtly increases the somatic and germline mutation burden. In contrast,
    tumors developed in individuals with a heterozygous mutation in the exonuclease
    domain of POLD1, including L474P, have an extremely high mutation rate (>100 mut/Mb)
    associated with signature SBS10d. We solved this contradiction through the observation
    that tumorigenesis involves somatic inactivation of the wildtype POLD1 allele.
    These results imply that exonuclease deficiency of polymerase delta has a recessive
    effect on mutation rate.@eng
  bibo_authorlist:
  - foaf_Person:
      foaf_givenName: Maria A.
      foaf_name: Andrianova, Maria A.
      foaf_surname: Andrianova
  - foaf_Person:
      foaf_givenName: Vladimir B.
      foaf_name: Seplyarskiy, Vladimir B.
      foaf_surname: Seplyarskiy
  - foaf_Person:
      foaf_givenName: Mariona
      foaf_name: Terradas, Mariona
      foaf_surname: Terradas
  - foaf_Person:
      foaf_givenName: Ana Beatriz
      foaf_name: Sánchez-Heras, Ana Beatriz
      foaf_surname: Sánchez-Heras
  - foaf_Person:
      foaf_givenName: Pilar
      foaf_name: Mur, Pilar
      foaf_surname: Mur
  - foaf_Person:
      foaf_givenName: José Luis
      foaf_name: Soto, José Luis
      foaf_surname: Soto
  - foaf_Person:
      foaf_givenName: Gemma
      foaf_name: Aiza, Gemma
      foaf_surname: Aiza
  - foaf_Person:
      foaf_givenName: Emma
      foaf_name: Borràs, Emma
      foaf_surname: Borràs
  - foaf_Person:
      foaf_givenName: Fyodor
      foaf_name: Kondrashov, Fyodor
      foaf_surname: Kondrashov
      foaf_workInfoHomepage: http://www.librecat.org/personId=44FDEF62-F248-11E8-B48F-1D18A9856A87
    orcid: 0000-0001-8243-4694
  - foaf_Person:
      foaf_givenName: Alexey S.
      foaf_name: Kondrashov, Alexey S.
      foaf_surname: Kondrashov
  - foaf_Person:
      foaf_givenName: Georgii A.
      foaf_name: Bazykin, Georgii A.
      foaf_surname: Bazykin
  - foaf_Person:
      foaf_givenName: Laura
      foaf_name: Valle, Laura
      foaf_surname: Valle
  bibo_doi: 10.1038/s41431-024-01598-8
  bibo_volume: 32
  dct_date: 2024^xs_gYear
  dct_identifier:
  - UT:001207703200001
  dct_isPartOf:
  - http://id.crossref.org/issn/1018-4813
  - http://id.crossref.org/issn/1476-5438
  dct_language: eng
  dct_publisher: Springer Nature@
  dct_title: Discovery of recessive effect of human polymerase δ proofreading deficiency
    through mutational analysis of POLD1-mutated normal and cancer cells@
  fabio_hasPubmedId: '38658779'
...