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Homologous recombination and maintenance of genome integrity: cancer and aging through the prism of human RecQ helicases.

Abstract
Homologous recombination (HR) is a genetic mechanism in somatic cells that repairs DNA double-strand breaks and restores productive DNA synthesis following disruption of replication forks. Although HR is indispensable for maintaining genome integrity, it must be tightly regulated to avoid harmful outcomes. HR-associated genomic instabilities arise in three human genetic disorders, Bloom syndrome (BS), Werner syndrome (WS), and Rothmund-Thomson syndrome (RTS), which are caused by defects in three individual proteins of the RecQ family of helicases, BLM, WRN, and RECQL4, respectively. Cells derived from persons with these syndromes display varying types of genomic instability as evidenced by the presence of different kinds of chromosomal abnormalities and different sensitivities to DNA damaging agents. Persons with these syndromes exhibit a variety of developmental defects and are predisposed to a wide range of cancers. WS and RTS are further characterized by premature aging. Recent research has shown many connections between all three proteins and the regulation of excess HR. Here, we illustrate the elaborate networks of BLM, WRN, and RECQL4 in regulating HR, and the potential mechanistic linkages to cancer and aging.
AuthorsKaren J Ouyang, Leslie L Woo, Nathan A Ellis
JournalMechanisms of ageing and development (Mech Ageing Dev) 2008 Jul-Aug Vol. 129 Issue 7-8 Pg. 425-40 ISSN: 0047-6374 [Print] Ireland
PMID18430459 (Publication Type: Journal Article, Review)
Chemical References
  • Exodeoxyribonucleases
  • Bloom syndrome protein
  • RECQL4 protein, human
  • DNA Helicases
  • RecQ Helicases
  • WRN protein, human
  • Werner Syndrome Helicase
Topics
  • Aging (genetics)
  • DNA Helicases (genetics, metabolism)
  • DNA Repair
  • DNA Repair-Deficiency Disorders (genetics)
  • Exodeoxyribonucleases (genetics, metabolism)
  • Genomic Instability
  • Humans
  • Neoplasms (genetics)
  • RecQ Helicases (genetics, metabolism)
  • Recombination, Genetic
  • Werner Syndrome Helicase

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