Lecture 11 Flashcards
What are four major problems of DNA replication?
Replication error, replication fork stalling, supercoiling of genomic DNA, & shortening of genomic DNA
Describe the process of initiation of DNA replication
Origin Recognition Complex (ORC) destabilizes replication origin and recruits a replicative helicase complex (MCM) to break apart and separate the strands of DNA. Replication Protein A (RPA) holds the replication bubble open.
Which DNA polymerase initiates DNA replication on both sides?
Polymerase alpha-primase
Which DNA polymerase replicates the leading strand?
Polymerase epsilon with the help of PCNA as a clamp to hold it to the DNA strand
Which DNA polymerase replicates the lagging strand?
Polymerase alpha-primase to Polymerase delta
How is the lagging strand replicated?
RNA primers produce Okazaki fragments along the DNA strand. RNase H removes the primers and allows for missing base pairs to be synthesized. FEN1 removes any additional displaced base pairs. DNA ligase fuses the newly formed DNA together
How does the DNA correct for mispaired bases?
Exonucleases correct mispaired bases by removing them and replacing them with correct bases
What is Meier-Gorlin syndrome?
It is caused by a mutation in one of several genes including ORC1, ORC4, ORC6, CDT1, and CDC6. It causes growth defects before birth that result in underdeveloped parts of the body and even dwarfism (normal intellect, however)
Which polymerases proofread replication errors?
Polymerases delta and epsilon
What happens during replication fork stalling?
DNA polymerase and helicase decouple from one another, causing helicase to continually open the double stranded DNA without DNA polymerase continually base pairing each strand (results in unpaired DNA)
What is ATR?
ATR (ataxia telangiectasia and Rad3-related protein) is a serine/threonine-specific protein kinase that is involved in sensing DNA damage and activating the DNA damage checkpoint, leading to cell cycle arrest
What is Seckel syndrome?
Mutations in ATR cause growth defects and mental retardation
What do topoisomerases do?
Topoisomerases prevent DNA from supercoiling by nicking and sealing DNA when it begins unwarranted coiling
How often do telomeres shorten?
Telomeres shorten with every cell division until they are critically short and trigger a permanent growth arrest called cellular senescence
What is idiopathic pulmonary fibrosis?
Pulmonary fibrosis is a disease in which tissue deep in your lungs becomes thick and stiff, or scarred, over time. The formation of scar tissue is called fibrosis