The Regulatory Interactions of p21 and PCNA in Human Breast Cancer
Abstract
Proliferating cell nuclear antigen (PCNA) is a multifunctional enzyme involved in multiple cellular processes including DNA replication and repair. During DNA replication, PCNA function as an accessory factor- for the DNA polymerases E arid and are part of a multiprotein DNA replication complex termed the DNA synthesome. Isolation and analysis of the of the DNA synthesomes from non-malignant and malignant breast cells has previously shown that replication fidelity is significantly reduced in malignant cells as compared to non-malignant cells. This reduction in replication fidelity in malignant cells is accompanied by a structural alteration to PCNA. In attempts to explain how this structural alteration to PCNA present in malignant cells could result in lowered replication fidelity, the ability PCNA present in malignant cells to interact with p21WAF1 was examined. Initially identified as a cyclin-dependent kinase inhibitor, p21WAF1 ability to inhibit DNA replication in response to DNA damage has been wall characterized. Interestingly, p21WAFl inhibits DNA replication by interacting with PCNA, and an inability of p21WAF1 to interact with the structurally altered PONA present in malignant cells could have tremendous mutagenic potential. However, research soon proved that the effects of this structural change to PCNA would not be so simple. Examination of the interaction of p21WAFl with PCNA revealed a third form of PCNA present in malignant cells that preferentially bound p21WAPl Elucidation of three isoforms of PCNA present in malignant breast cells may therefore represent signaling events that link DNA replication to DNA repair through structural alterations to PCNA.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA408176
Entities
People
- Derek Hoelz
- Linda Malkas
Organizations
- University of Maryland, Baltimore