Replication is not as continuous as once thought, with DNA damage frequently stalling replication forks. Aberrant repair of stressed replication forks can result in cell death or genome instability and resulting transformation to malignancy. Stressed replication forks are most commonly repaired via homologous recombination (HR), which begins with end resection, mediated by exonuclease complexes, one of which contains Exo1. However, Exo1 requires free DNA ends upon which to act, and these are not commonly present in non-reversed stalled replication forks. To generate a free DNA end, stalled replication forks must therefore be cleaved. While several candidate endonucleases have been implicated in cleavage of stalled replication forks to permit end resection, the identity of such an endonuclease remains elusive. Here we show that the endonuclease EEPD1 cleaves replication forks at the junction between the lagging parental strand and the unreplicated DNA parental double strands. This cleavage creates the structure that Exo1 requires for end resection and HR initiation. We observed that EEPD1 and Exo1 interact constitutively, and Exo1 repairs stalled replication forks poorly without EEPD1. Thus, EEPD1 performs a gatekeeper function for replication fork repair by mediating the fork cleavage that permits initiation of HR-mediated repair and restart of stressed forks.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2iGgVcr
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
-
Related Articles Anatomic parameters of the sacral lamina for osteosynthesis in transverse sacral fractures. Surg Radiol Anat....
-
Background Hyperthyroidism is associated with increased thrombotic risk. As contact system activation through formation of neutrophil extrac...
-
BACKGROUND AND PURPOSE: Dengue is a common arboviral disease, which uncommonly involves the brain. There has been a recent surge in dengu...
-
Noncaloric sweeteners (NCS) are food additives used to provide sweetness without adding calories. Their consumption has become more widespre...
-
from Imaging via alkiviadis.1961 on Inoreader https://ift.tt/2v5fvQ4
-
Abstract Purpose Investigate in patients with metastatic and/or irresectable colorectal cancer treated with systemic treatment with cape...
-
Abstract Objectives (1) To illustrate and describe the main types of pancreatic surgery; (2) to discuss the normal findings after pancre...
-
A 67-year-old woman was referred to our hospital because of gradually increasing dyspnoea on exertion for 6 months. Chest CT scan showed sub...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου