Cryogenic electron microscopy (cryo-EM) has enabled researchers to study how the DNA replication machinery assembles at sites where it is damaged.Cellular DNA is continually exposed to both endogenous and exogenous damaging agents such as reactive oxygen species and ultraviolet radiation.To reduce the biological consequences of DNA damage, all living organisms have developed mechanisms to tolerate and repair DNA damage to try to ensure that genetic information is inherited accurately.One of those mechanisms, called translesion synthesis (TLS), allows DNA replication to proceed through unrepaired DNA damage.TLS involves high-precision DNA synthesis enzymes (replicative DNA polymerases) that are temporarily replaced with specialized low-fidelity TLS polymerases that can ensure cell survival at the expense of the introduction of mutations.The mutagenic and synthetic translession activity of TLS polymerases can cause normal cells to become cancerous or cancer cells to become resistant to drugs.The Pol TLS polymerase of the Y family is capable of DNA synthesis through various damaged bases and is recruited into DNA lesions by proliferation of cellular nuclear antigen (PCNA).Previous studies have shown that PCNA is regulated by ubiquitination."The addition of a single ubiquitin molecule at PCNA lysine 164 (K164) residue facilitates the recruitment and retention of TLS polymerases at sites of damage, but the structural basis of the interaction between these polymerases and ubiquitinated PCNA is poor. known, "the researchers noted.The group of scientists has been collaborating with the laboratory led by Samir Hamdan, an expert in single-molecule analysis of human DNA replication, since 2018. They have been using cryo-EM to investigate the three-dimensional structure and function of the complexes. of key proteins involved in DNA replication and repair.Their latest study describes cryo-MS reconstructions of full-length human Pol bound to DNA, an incoming nucleotide, and unmodified PCNA or monobiquitylated PCNA, with near-atomic resolution.They found that, in the absence of DNA, the structure of Pol bound to PCNA is very flexible, suggesting that binding to DNA is required to form a rigid and active complex.“Our data provide a structural framework to explain how PCNA recruits a TLS family Y polymerase at sites of DNA damage.By understanding the interactions between the proteins that make up these complexes and how they are regulated, we can identify ways to reduce or increase their function for medical applications ”, they concluded.Because we all need health ... ConSalud.esA faster "code breaker" for analyzing human DNAA combined lighter with microneedles for administering DNA vaccinesEC Green Light for MSD's 15-Valente Pneumococide Conjugate VaccineSinopharm booster vaccine, less effective against OmicronAMA Foundation announces one more year 124 scholarships for the training of health professionalsMAD: C / Ferrocarril 18, 1ª planta, 28045, MadridBCN: Av.Diagonal 474, 1st floor, 08006 BarcelonaReceive the ConSalud.es NewsletterEvery day and free of charge the newsletter with all the information of the health sector