scispace - formally typeset
Journal ArticleDOI

Regulation of PCNA-protein interactions for genome stability.

TLDR
Control of PCNA–protein interactions is multilayered and involves post-translational modifications, in particular ubiquitylation, accessory factors and regulated degradation ofPCNA-associated proteins, which allows cells to maintain a fine-tuned balance between replication fidelity and processivity in response to DNA damage.
Abstract
Proliferating cell nuclear antigen (PCNA) has a central role in promoting faithful DNA replication, providing a molecular platform that facilitates the myriad protein-protein and protein-DNA interactions that occur at the replication fork. Numerous PCNA-associated proteins compete for binding to a common surface on PCNA; hence these interactions need to be tightly regulated and coordinated to ensure proper chromosome replication and integrity. Control of PCNA-protein interactions is multilayered and involves post-translational modifications, in particular ubiquitylation, accessory factors and regulated degradation of PCNA-associated proteins. This regulatory framework allows cells to maintain a fine-tuned balance between replication fidelity and processivity in response to DNA damage.

read more

Citations
More filters
Journal ArticleDOI

Causes and consequences of replication stress.

TL;DR: In this paper, the kinase ATR (ATM- and Rad3-related) stabilizes and helps to restart stalled replication forks, avoiding the generation of DNA damage and genome instability.
Journal ArticleDOI

Replication stress and cancer

TL;DR: The link between persistent replication stress and tumorigenesis is discussed, with the goal of shedding light on the mechanisms underlying the initiation of an oncogenic process, which should open up new possibilities for cancer diagnostics and treatment.
Journal ArticleDOI

Regulation of DNA double-strand break repair by ubiquitin and ubiquitin-like modifiers

TL;DR: Findings have revealed compelling insights into the complex mechanisms by which ubiquitin and UBLs regulate protein interactions with DSB sites to promote accurate lesion repair and protection of genome integrity in mammalian cells, and offer new therapeutic opportunities for diseases linked to genetic instability.
Journal ArticleDOI

Forging Ahead through Darkness: PCNA, Still the Principal Conductor at the Replication Fork

TL;DR: This work has shown that through its many protein interactions and various post-translational modifications, PCNA has far-reaching impacts on a myriad of cellular functions.
Journal ArticleDOI

PCNA: a silent housekeeper or a potential therapeutic target?

TL;DR: New developments in its protein interactions, trimer formation, and signaling regulation that open the door to possible therapeutic targeting of PCNA are discussed.
References
More filters
Journal ArticleDOI

The DNA Damage Response: Making It Safe to Play with Knives

TL;DR: This review will focus on how the DDR controls DNA repair and the phenotypic consequences of defects in these critical regulatory functions in mammals.
Journal ArticleDOI

RAD6 -dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO

TL;DR: It is shown that UBC9, a small ubiquitin-related modifier (SUMO)-conjugating enzyme, is also affiliated with this pathway and that proliferating cell nuclear antigen (PCNA) is a substrate, and that damage-induced PCNA ubiquitination is elementary for DNA repair and occurs at the same conserved residue in yeast and humans.
Journal ArticleDOI

PCNA, the Maestro of the Replication Fork

TL;DR: Proliferating cell nuclear antigen -a cofactor of DNA polymerases that encircles DNA-orchestrates several of these functions by recruiting crucial players to the replication fork, indicating that these interactions do not occur simultaneously during replication.
Journal ArticleDOI

Systematic and Quantitative Assessment of the Ubiquitin-Modified Proteome

TL;DR: The human ubiquitin-modified proteome is characterized using a monoclonal antibody that recognizes diglycine (diGly)-containing isopeptides following trypsin digestion and it is demonstrated that quantitative diGly proteomics can be utilized to identify substrates for cullin-RING ubiquitIn ligases.
Journal ArticleDOI

The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.

TL;DR: Recombinant human DNA polymerase η corrects the inability of XP-V cell extracts to carry out DNA replication by bypassing thymine dimers on damaged DNA, indicating that DNA polymerases η could be the XPV gene product.
Related Papers (5)